Molecular Neurobiology

, Volume 18, Issue 1, pp 35–86 | Cite as

The diversity of GABAA receptors

Pharmacological and electrophysiological properties of GABAA channel subtypes
  • Wulf Hevers
  • Hartmut Lüddens


The amino acid γ-aminobutyric-acid (GABA) prevails in the CNS as an inhibitory neurotrans-mitter that mediates most of its effects through fast GABA-gated Cl-channels (GABAAR). Molecular biology uncovered the complex subunit architecture of this receptor channel, in which a pentameric assembly derived from five of at least 17 mammalian subunits, grouped in the six classes α, β, γ, δ, ε, and ρ, permits a vast number of putative receptor isoforms. The subunit composition of a particular receptor determines the specific effects of allosterical modulators of the GABAARs like benzodiazepines (BZs), barbiturates, steroids, some convulsants, polyvalent cations, and ethanol. To understand the physiology and diversity of GABAARs, the native isoforms have to be identified by their localization in the brain and by their pharmacology. In heterologous expression systems, channels require the presence of α, β, and γ subunits in order to mimic the full repertoire of native receptor responses to drugs, with the BZ pharmacology being determined by the particular α and γ subunit variants. Little is known about the functional properties of the β, δ, and ε subunit classes and only a few receptor subtype-specific substances like loreclezole and furosemide are known that enable the identification of defined receptor subtypes. We will summarize the pharmacology of putative receptor isoforms and emphasize the characteristics of functional channels. Knowledge of the complex pharmacology of GABAARs might eventually enable site-directed drug design to further our understanding of GABA-related disorders and of the complex interaction of excitatory and inhibitory mechanisms in neuronal processing.

Index Entries

GABAA benzodiazepines electrophysiology recombinant receptors 


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  1. Akaike N., Tokutomi N. and Ikemoto Y. (1990) Augmentation of GABA-induced current in frog sensory neurons by pentobarbital.Am. J. Physiol. 258, C452–460.PubMedGoogle Scholar
  2. Alkon, D. L., Sanchez Andres J. V., Ito, E., Oka, K., Yoshioka T. and Collin, C. (1992) Long-term transformation of an inhibitory into an excitatory GABAergic synaptic response.Proc. Natl. Acad. Sci. USA 89, 11,862–11,866.CrossRefGoogle Scholar
  3. Allan A. M. and Harris R. A. (1986) γ-aminobutyric acid and alcohol actions: neurochemical studies of long sleep and short sleep mice.Life Sci. 39, 2005–2015.PubMedCrossRefGoogle Scholar
  4. Amin J. and Weiss D. S. (1993) GABAA receptor needs two homologous domains of the β-subunit for activation by GABA but not by pentobarbital [see comments].Nature 366, 565–569.PubMedCrossRefGoogle Scholar
  5. Angelotti T. P. and Macdonald R. L. (1993) Assembly of GABAA receptor subunits: α1 β1 and α1 β1 γ2S subunits produce unique ion channels with dissimilar single-channel properties.J. Neurosci. 13, 1429–1440.PubMedGoogle Scholar
  6. Angelotti T. P., Tan F., Chahine K. G. and Macdonald R. L. (1992) Molecular and electrophysiological characterization of a allelic variant of the rat α 6 GABAA receptor subunit.Brain Res. Mol. Brain Res. 16, 173–178.PubMedCrossRefGoogle Scholar
  7. Angelotti T. P., Uhler M. D. and Macdonald R. L. (1993) Assembly of GABAA receptor subunits: analysis of transient single-cell expression utilizing a fluorescent substrate/marker gene technique.J. Neurosci. 13, 1418–1428.PubMedGoogle Scholar
  8. Angelotti T. P., Uhler M. D. and Macdonald R. L. (1993) Enhancement of recombinant γ-aminobutyric acid type A receptor currents by chronic activation of cAMP-dependent protein kinase.Mol. Pharmacol. 44, 1202–1210.PubMedGoogle Scholar
  9. Arbilla S., Allen, J., Wick, A. and Langer S. Z. (1986) High affinity [3H]zolpidem binding in the rat brain: an imidazopyridine with agonist properties at central benzodiazepine receptors.Eur. J. Pharmacol 130, 257–263.PubMedCrossRefGoogle Scholar
  10. Asano T. and Ogasawara N. (1982) Stimulation of GABA receptor binding by barbiturates.Eur. J. Pharmacol. 77, 355–357.PubMedCrossRefGoogle Scholar
  11. Asano, T., Sakakibara, J. and Ogasawara, N. (1983) Molecular sizes of photolabeled GABA and benzodiazepine receptor proteins are identical.FEBS Lett. 151, 277–280.PubMedCrossRefGoogle Scholar
  12. Ashton D., Fransen J., Heeres J., Clincke G. H. and Janssen P. A. (1992) In vivo studies on the mechanism of action of the broad spectrum anticonvulsant loreclezole.Epilepsy Res. 11, 27–36.PubMedCrossRefGoogle Scholar
  13. Avoli, M. (1992) Synaptic activation of GABAA receptors causes a depolarizing potential under physiological conditions in rat hippocampla pyramidal cells.Eur. J. Neurosci. 4, 16–26.PubMedCrossRefGoogle Scholar
  14. Avoli, M. and Perreault, P. (1987) A GABAergic depolarizing potential in the hippocampus disclosed by the convulsant 4-aminopyridine.Brain Res. 400, 191–195.PubMedCrossRefGoogle Scholar
  15. Backus K. H., Arigoni M., Drescher U., Scheurer L., Malherbe P., Mohler H. and Benson J. A. (1993) Stoichiometry of a recombinant GABAA receptor deduced from mutation-induced rectification.Neuroreport 5, 285–288.PubMedCrossRefGoogle Scholar
  16. Ballanyi K. and Grafe P. (1985) An intracellular analysis of γ-aminobutyric-acid-associated ion movements in rat sympathetic neurones.J. Physiol. Lond. 365, 41–58.PubMedGoogle Scholar
  17. Barker, J. L., Harrison, N. L., Lange, G. D. and Owen, D. G. (1987) Potentiation of γ-aminobutyric-acid-activated chloride conductance by a steroid anaesthetic in cultured rat spinal neurones.J. Physiol. Lond. 386, 485–501.PubMedGoogle Scholar
  18. Barker, J. L., Owen D. G. and Segal, M. (1984) GABA actions on the excitability of cultured CNS neurons.Neurosci. Lett. 47, 313–318.PubMedCrossRefGoogle Scholar
  19. Basile A. S., Bolger G. T., Lueddens H. W. and Skolnick P. (1989) Electrophysiological actions of Ro5-4864 on cerebellar Purkinje neurons: evidence for “peripheral” benzodiazepine receptor-mediated depression.J. Pharmacol. Exp. Ther. 248, 463–469.PubMedGoogle Scholar
  20. Bateson, A. N., Lasham, A. and Darlison, M. G. (1991) γ-Aminobutyric acidA receptor heterogeneity is increased by alternative splicing of a novel β-subunit gene transcript.J. Neurochem. 56, 1437–1440.PubMedCrossRefGoogle Scholar
  21. Baude, A., Sequier, J. M., McKernan, R. M., Olivier, K. R. and Somogyi, P. (1992) Differential subcellular distribution of the α6 subunit versus the α1 and β2/3 subunits of the GABAA/benzodiazepine receptor complex in granule cells of the cerebellar cortex.Neuroscience 51, 739–748.PubMedCrossRefGoogle Scholar
  22. Benke D., Fritschy J. M., Trzeciak A., Bannwarth W. and Mohler H. (1994) Distribution, prevalence, and drug binding profile of γ-aminobutyric acid type A receptor subtypes differing in the β-subunit variant.J. Biol. Chem. 269, 27,100–27,107.Google Scholar
  23. Benke D., Mertens S., Trzeciak A., Gillessen D. and Mohler H. (1991) GABAA receptors display association of γ2-subunit with α1- and β2/3-subunits.J. Biol. Chem. 266, 4478–4483.PubMedGoogle Scholar
  24. Benke, D., Mertens S., Trzeciak A., Gillessen D. and Mohler, H. (1991) Identification and immunohis-tocistochemical mapping of GABAA receptor subtypes containing the δ-subunit in rat brain.FEBS Lett. 283, 145–149.PubMedCrossRefGoogle Scholar
  25. Betz H. (1990) Ligand-gated ion channels in the brain: the amino acid receptor superfamily.Neuron 5, 383–392.PubMedCrossRefGoogle Scholar
  26. Blair L. A., Levitan E. S., Marshall J., Dionne, V. E. and Barnard, E. A. (1988) Single subunits of the GABAA receptor form ion channels with properties of the native receptor.Science 242, 577–579.PubMedCrossRefGoogle Scholar
  27. Blanchard, J. C. and Julou, L. (1983) Suriclone: a new cyclopyrrolone derivative recognizing receptors labeled by benzodiazepines in rat hippocampus and cerebellum.J. Neurochem. 40, 601–607.PubMedCrossRefGoogle Scholar
  28. Bloom F. E. and Iversen L. L. (1971) Localizing3H-GABA in nerve terminals of rat cerebral cortex by electron microscopic autoradiography.Nature 229, 628–630.PubMedCrossRefGoogle Scholar
  29. Bonetti E. P., Burkhard W. P., Gabl M., Hunkeler W., Lorez H.-P., et al. (1989) Ro 15-4513: partial inverse agonism at the BZR and interactions with ethanol.Pharmacol. Biochem. Behav. 31, 733–749.CrossRefGoogle Scholar
  30. Bormann J. (1988) Electrophysiology of GABAA and GABAB receptor subtypes.Trends Neurochem. Sci. 11, 112–116.CrossRefGoogle Scholar
  31. Bormann J. and Clapham D. E. (1985) γ-Aminobutyric acid receptor channels in adrenal chromaffin cells: a patch-clamp study.Proc. Natl. Acad. Sci. USA 82, 2168–2172.PubMedCrossRefGoogle Scholar
  32. Bormann J. and Feigenspan A. (1995) GABAc receptors.Trends Neurosci. 18, 515–519.PubMedCrossRefGoogle Scholar
  33. Bormann J., Hamill O. P. and Sakmann B. (1987) Mechanism of anion permeation through channels gated by glycine and γ-aminobutyric acid in mouse cultured spinal neurones.J. Physiol. Lond. 385, 243–286.PubMedGoogle Scholar
  34. Bowery N. G. (1993) GABAB receptor pharmacology.Annu. Rev. Pharmacol. Toxicol. 33, 109–147.PubMedGoogle Scholar
  35. Bowery, N. (1989) GABAB receptors and their significance in mammalian pharmacology.Trends Pharmacol. Sci. 10, 401–407.PubMedCrossRefGoogle Scholar
  36. Bradford H. F. (1995) Glutamate, GABA and epilepsy.Prog. Neurobiol. 47, 477–511.PubMedCrossRefGoogle Scholar
  37. Braestrup C. and Nielsen M. (1981) [3H]Propyl β-carboline-3-carboxylate as a selective radioligand for the BZ1 benzodiazepine receptor subclass.J. Neurochem. 37, 333–341.PubMedCrossRefGoogle Scholar
  38. Braestrup, C., Honore, T., Nielsen, M., Petersen, E. N. and Jensen, L. H. (1984) Ligands for benzodiazepine receptors with positive and negative efficacy.Biochem. Pharmacol. 33, 859–862.PubMedCrossRefGoogle Scholar
  39. Braestrup, C., Nielsen, M., Honore, T., Jensen, L. H. and Petersen, E. N. (1983) Benzodiazepine receptor ligands with positive and negative efficacy.Neuropharmacology 22, 1451–1457.PubMedCrossRefGoogle Scholar
  40. Braestrup, C., Schmiechen, R., Neef, G., Nielsen, M. and Petersen, E. N. (1982) Interaction of convulsive ligands with benzodiazepine receptors.Science 216, 1241–1243.PubMedCrossRefGoogle Scholar
  41. Breese G. R., Morrow A. L., Simson P. E., Criswell H. E., McCown T. J., Duncan, G. E. and Keir W. J. (1993) The neuroanatomical specificity of ethanol action on ligand-gated ion channels: a hypothesis.Alcohol. Alcoholism Suppl. 2, 309–313.Google Scholar
  42. Brown M. J. and Bristow D. R. (1996) Molecular mechanisms of benzodiazepine-induced down-regulation of GABAA receptor α1 subunit protein in rat cerebellar granule cells.Br. J. Pharmacol. 118, 1103–1110.PubMedGoogle Scholar
  43. Buhr A., Baur R., Malherbe P. and Sigel E. (1996) Point mutations of the α1β2γ2 γ-aminobutyric acidA receptor affecting modulation of the channel by ligands of the benzodiazepine binding site.Mol. Pharmacol. 49, 1080–1084.PubMedGoogle Scholar
  44. Burgard E. C., Tietz E. I., Neelands T. R. and Macdonald R. L. (1996) Properties of recombinant γ-iminobutyric acidA receptor isoforms containing the α5 subunit subtype.Mol. Pharmacol. 50, 119–127.PubMedGoogle Scholar
  45. Callachan, H., Cottrell, G. A., Hather, N. Y., Lambert, J. J., Nooney, J. M. and Peters, J. A. (1987) Modulation of the GABAA receptor by progesterone metabolites.Proc. R. Soc. Lond. B. Biol. Sci. 231, 359–369.PubMedGoogle Scholar
  46. Caruncho, H. J. and Costa, E. (1994) Double-immunolabelling analysis of GABAA receptor subunits in inlabel-fracture replicas of cultured rat cerebellar granule cells.Rec. Channels 2, 143–153.Google Scholar
  47. Casalotti S. O., Stephenson F. A. and Barnard E. A. (1986) Separate subunits for agonist and benzodiazepine binding in the γ-aminobutyric acidA receptor oligomer.J. Biol. Chem. 261, 15,013–15,016.Google Scholar
  48. Cash D. J. and Subbarao K. (1988) Different effects of pentobarbital on two γ-aminobutyrate receptors from rat brain: channel opening, desensitization, and an additional conformational change.Biochemistry 27, 4580–4590.PubMedCrossRefGoogle Scholar
  49. Casida J. E. (1993) Insecticide action at the GABA-gated chloride channel: recognition, progress, and prospects.Arch. Insect Biochem. Physiol. 22, 13–23.PubMedCrossRefGoogle Scholar
  50. Celentano J. J., Gibbs T. T. and Farb D. H. (1988) Ethanol potentiates GABA- and glycine-induced chloride currents in chick spinal cord neurons.Brain Res. 455, 377–380.PubMedCrossRefGoogle Scholar
  51. Chambon, J. P., Feltz, P., Heaulme, M., Restle, S., Schlichter, R., Biziere, K. and Wermuth, C. G. (1985) An arylaminopyridazine derivative of γ-aminobutyric acid (GABA) is a selective and competitive antagonist at the GABAA receptor site.Proc. Natl. Acad. Sci. USA 82, 1832–1836.PubMedCrossRefGoogle Scholar
  52. Chang Y. C., Wang R. P., Barot S. and Weiss D. S. (1996) Stoichiometry of a recombinant GABAA receptor.J. Neurosci. 16, 5415–5424.PubMedGoogle Scholar
  53. Cherubini, E., Gaiarsa, J. L. and Ben Ari, Y. (1991) GABA: an excitatory transmitter in early postnatal life.Trends Neurosci. 14, 515–519.PubMedCrossRefGoogle Scholar
  54. Choi, D. W., Farb D. H. and Fischbach, G. D. (1977) Chlordiazepoxide selectively augments GABA action in spinal cord cell cultures.Nature 269, 342–344.CrossRefGoogle Scholar
  55. Choi, D. W., Farb, D. H. and Fischbach, G. D. (1981a) Chloriazepoxide selectively potentiates GABA conductance of spinal cord and sensory neurons in cell culture.J. Neurophysiol. 45, 621–631.PubMedGoogle Scholar
  56. Choi, D. W., Farb D. H. and Fischbach, G. D. (1981b) GABA-mediated synaptic potentials in chick spinal cord and sensory neurons.J. Neurophysiol. 45, 632–643.PubMedGoogle Scholar
  57. Concas A., Santoro G., Serra M., Sanna E. and Biggio G. (1991) Neurochemical action of the general anaesthetic profofol on the chloride ion channel coupled with GABAA receptors.Brain Res. 542, 225–232.PubMedCrossRefGoogle Scholar
  58. Concas, A., Serra, M., Santoro, G., Maciocco, E., Coccheddu, T. and Biggio, G. (1994) The effect of cyclopyrrolones on GABAA receptor function is different from that of benzodiazepines.Naunyn-Schmied. Arch Pharmacol. 350, 294–300.CrossRefGoogle Scholar
  59. Connolly C. N., Wooltorton J. R. A., Smart T. G. and Moss S. J. (1996) Subcellular localization of γ-aminobutyric acid type A receptors is determined by receptor β subunits.Proc. Nat. Acad. Sci. USA 93, 9899–9904.PubMedCrossRefGoogle Scholar
  60. Connolly, C. N., Krishek, B. J., McDonald, B. J., Smart, T. G. and Moss, S. J. (1996) Assembly and cell surface expression of heteromeric and homomeric γ-aminobutyric acid type A receptors.J. Biol. Chem. 271, 89–96.PubMedCrossRefGoogle Scholar
  61. Corda M. G., Giorgi O., Longoni B., Ongini E., Montaldo S. and Biggio G. (1988) Preferential affinity of3H-2-oxo-quazepam for type I benzodiazepine recognition sites in the human brain.Life Sci. 42, 189–197.PubMedCrossRefGoogle Scholar
  62. Corpechot, C., Robel, P., Axelson, M., Sjovall, J. and Baulieu, E. E. (1981) Characterization and measurement of dehydroepiandrosterone sulfate in rat brain.Proc. Natl. Acad. Sci. USA 78, 4704–4707.PubMedCrossRefGoogle Scholar
  63. Corpechot, C., Synguelakis, M., Talha, S., Axelson, M., Sjovall, J., et al. (1983) Pregnenolone and its sulfate ester in the rat brain.Brain Res. 270, 119–125.PubMedCrossRefGoogle Scholar
  64. Cottrell, G. A., Lambert, J. J. and Peters, J. A. (1987) Modulation of GABAA receptor activity by alphaxalone.Br. J. Pharmacol. 90, 491–500.PubMedGoogle Scholar
  65. Criswell H. E., Simson P. E., Knapp D. J., Devaud L. L., McCown T. J., et al. (1995) Effect of zolpidem on γ-aminobutyric acid (GABA)-induced inhibition predicts the interaction of ethanol with GABA on individual neurons in several rat brain regions.J. Pharmacol. Exp. Ther. 273, 526–236.PubMedGoogle Scholar
  66. Culiat C. T., Stubbs L. J., Montgomery C. S., Russell L. B. and Rinchik E. M. (1994) Phenotypic consequences of deletion of the γ3, α5, or β3 subunit of the type A γ-aminobutyric acid receptor in mice.Proc. Natl. Acad. Sci. USA 91, 2815–2818.PubMedCrossRefGoogle Scholar
  67. Culiat, C. T., Stubbs L. J., Woychik R. P., Russell, L. B., Johnson, D. K. and Rinchik E. M. (1995) Deficiency of the β3 subunit of the type A γ-aminobutyric acid receptor causes cleft palate in mice.Nat. Genet. 11, 344–346.PubMedCrossRefGoogle Scholar
  68. Culiat, C. T., Stubbs, L., Nicholls, R. D., Montgomery, C. S., Russell, L. B., Johnson, D. K. and Rinchik, E. M. (1993) Concordance between isolated cleft palate in mice and alterations within a region including the gene encoding the β3-subunit of the type-A γ-aminobutyric acid receptor.Proc. Natl. Acad. Sci. USA 90, 5105–5109.PubMedCrossRefGoogle Scholar
  69. Cutting, G. R., Curristin, S., Zoghbi H., O'Hara, B., Seldin M. F. and Uhl, G. R. (1992) Identification of a putative γ-aminobutyric acid (GABA) receptor subunit ρ2 cDNA and colocalization of the genes encoding ρ2 (GABRR2) and ρ1 (GABR1) to human chromosome 6q14-q21 and mouse chromosome 4.Genomics 12, 801–806.PubMedCrossRefGoogle Scholar
  70. Cutting, G. R., Lu L., Ohara, B. F., Kasch, L. M., Montrose-Rafizadeh, C., et al. (1991) Cloning of the γ-aminobutyric acid (GABA) ρ1 cDNA: a GABA receptor subunit highly expressed in the retina.Proc. Natl. Acad. Sci. USA 88, 2673–2677.PubMedCrossRefGoogle Scholar
  71. Darlison M. G. and Albrecht B. E. (1995) GABAA Receptor Subtypes: Which, Where and Why.Sem. Neurosci. 7, 115–126.CrossRefGoogle Scholar
  72. Davidoff R. A. (1973) Alcohol and presynaptic inhibition in an isolated spinal cord preparation.Arch. Neurol. 28, 60–63.PubMedGoogle Scholar
  73. Davies P. A., Hanna M. C., Hales T. G. and Kirkness E. F. (1997) Insensitivity to anesthetic agents conferred by a class of GABAA receptor subunit.Nature 385, 820–823.PubMedCrossRefGoogle Scholar
  74. De Deyn P. P., Marescau B. and Macdonald R. L. (1990) Epilepsy and the GABA-hypothesis a brief review and some examples.Acta. Neurol. Belg. 90, 65–81.PubMedGoogle Scholar
  75. DeBlas A. L. (1996) Brain GABAA receptors studied with subunit-specific antibodies.Mol. Neurobiol. 12, 55–71.CrossRefGoogle Scholar
  76. Deitrich R. A., Dunwiddie T. V., Harris R. A. and Erwin V. G. (1989) Mechanism of action of ethanol: initial central nervous system actions.Pharmacol. Rev. 41, 489–537.PubMedGoogle Scholar
  77. Deng L., Ransom R. W. and Olsen R. W. (1986) [3H]muscimol photolabels the γ-aminobutyric acid receptor binding site on a peptide subunit distinct from that labeled with benzodiazepines.Biochem. Biophys. Res. Commun. 138, 1308–1314.PubMedCrossRefGoogle Scholar
  78. Devaud L. L. and Morrow A. L. (1994) Effects of chronic ethanol administration on [3H]zolpidem binding in rat brain.Eur. J. Pharmacol. 267, 243–247.PubMedCrossRefGoogle Scholar
  79. Devaud L. L., Smith F. D., Grayson D. R. and Morrow A. L. (1995) Chronic ethanol consumption differentially alters the expression of γ-aminobutyric acidA receptor subunit mRNAs in rat cerebral cortex: competitive, quantitative reverse transcriptase-polymerase chain reaction analysis.Mol. Pharmacol. 48, 861–868.PubMedGoogle Scholar
  80. Doble A. and Martin I. L. (1992) Multiple benzodiazepine receptors: no reason for anxiety.Trends Pharmacol. Sci. 13, 76–81.PubMedCrossRefGoogle Scholar
  81. Dockhorn R. J. and Dockhorn D. W. (1996) Zolpidem in the treatment of short-term insomnia: a randomized, double-blind, placebo-controlled clinical trial.Clin. Neuropharmacol. 19, 333–340.PubMedCrossRefGoogle Scholar
  82. Draguhn A., Verdron T. A., Ewert M., Seeburg P. H. and Sakmann B. (1990) Functional and molecular distinction between recombinant rat GABAA receptor subtypes by Zn2+.Neuron 5, 781–788.PubMedCrossRefGoogle Scholar
  83. Drew, C. A. and Johnson, G. A. (1992) Bicucullineand baclofen-insensitive γ-aminobutyric acid binding to rat cerebellar membranes.J. Neurochem. 58, 1087–1092.PubMedCrossRefGoogle Scholar
  84. Drew, C. A., Johnston, G. A. and Weatherby, R. P. (1984) Bicuculline-insensitive GABA receptors: studies on the binding of (−)-baclofen to rat cerebellar membranes.Neurosci. Lett. 52, 317–321.PubMedCrossRefGoogle Scholar
  85. Ducic I., Caruncho H. J., Zhu W. J., Vicini S. and Costa E. (1995) γ-Aminobutyric acid gating of C1-channels in recombinant GABAA receptors.J. Pharmacol. Exp. Ther. 272, 438–445.PubMedGoogle Scholar
  86. Ducic I., Puia G., Vicini S. and Costa E. (1993) Triazolam is more efficacious than diazepam in a broad spectrum of recombinant GABAA receptors.Eur. J. Pharmacol. 244, 29–35.PubMedCrossRefGoogle Scholar
  87. Duncalfe L. L., Carpenter M. R., Smillie L. B., Martin I. L. and Dunn S. M. J. (1996) The major site of photoaffinity labeling of the γ-aminobutyric acid type a receptor by [3H] flunitrazepam is histidine 102 of the α subunit.J. Biol. Chem. 271, 9209–9214.PubMedCrossRefGoogle Scholar
  88. Duncalfe, L. L. and Dunn, S. M. J. (1996) Mapping of GABAA receptor sites that are photoaffinity-labelled by [H-3] flunitrazepam and [3H]Ro 15-4513.Eur. J. Pharmacol. 298, 313–319.PubMedCrossRefGoogle Scholar
  89. Ebert B., Wafford K. A., Whitting P. J., Krogsgaard Larsen P. and Kemp J. A. (1994) Molecular pharmacology of γ-aminobutyric acid type A receptor agonists and partial agonists in oocytes injected with different α, β, and γ receptor subunit combinations.Mol. Pharmacol. 46, 957–963.PubMedGoogle Scholar
  90. Enz, R., Brandstatter, J. H., Hartveit, E., Wassle, H. and Bormann, J. (1995) Expression of GABA receptor rho 1 and rho 2 subunits in the retina and brain of the rat.Eur. J. Neurosci. 7, 1495–1501.PubMedCrossRefGoogle Scholar
  91. Evoniuk, G., Moody, E. J. and Skolnick, P. (1989) Ultraviolet irradiation selectively disrupts the γ-aminobutyric acid/benzodiazepine receptor-linked chloride ionophore.Mol. Pharmacol. 35, 695–700.PubMedGoogle Scholar
  92. Facklam, M., Schoch, P. and Haefely, W. E. (1992) Relationship between benzodiazepine receptor occupancy and potentiation of γ-aminobutyric acid-stimulated chloride flux in vitro of four ligands of differing intrinsic efficacies.J. Pharmacol. Exp. Ther. 261, 1106–1112.PubMedGoogle Scholar
  93. Faure Halley C., Graham D., Arbilla S. and Langer S. Z. (1993) Expression and properties of recombinant α1β2γ2 and α5β2γ2 forms of the rat GABAA receptor.Eur. J. Pharmacol. 246, 283–287.CrossRefGoogle Scholar
  94. Feigenspan A. and Bormann J. (1994) Differential pharmacology of GABAA and GABAC receptors on rat retinal bipolar cells.Eur. J. Pharmacol. 288, 97–104.PubMedCrossRefGoogle Scholar
  95. Feigenspan A., Wassle H. and Bormann J. (1993) Pharmacology of GABA receptor Cl channels in rat retinal bipolar cells.Nature 361, 159–162.PubMedCrossRefGoogle Scholar
  96. Franks N. P. and Lieb W. R. (1994) Molecular and cellular mechanisms of general anaesthesia.Nature 367, 607–614.PubMedCrossRefGoogle Scholar
  97. Fraser A. D. (1996) New drugs for the treatment of epilepsy.Clin. Biochem. 29, 97–110.PubMedCrossRefGoogle Scholar
  98. Freund R. K. and Palmer M. R. (1996) 8-Bromo-cAMP mimics β-adrenergic sensitization of GABA responses to ethanol in cerebellar Purkinje neurons in vivo.Alcoholism-Clin. Exp. Res. 20, 408–412.CrossRefGoogle Scholar
  99. Fritschy J. M. and Mohler H. (1995) GABAA-receptor heterogeneity in the adult rat brain: differential regional and cellular distribution of seven major subunits.J. Comp. Neurol. 359, 154–194.PubMedCrossRefGoogle Scholar
  100. Fritschy J. M., Benke D., Mertens S., Oertel W. H., Bachi T. and Mohler, H. (1992) Five subtypes of type A γ-aminobutyric acid receptors identified in neurons by double and triple immunofluorescence staining with subunit-specific antibodies.Proc. Natl. Acad. Sci. USA 89, 6726–6730.PubMedCrossRefGoogle Scholar
  101. Fritschy, J. M., Paysan, J., Enna, A. and Mohler, H. (1994) Switch in the expression of rat GABAA-receptor subtypes during postnatal development: an immunohistochemical study.J. Neurosci. 14, 5302–5324.PubMedGoogle Scholar
  102. Gage P. W. and Robertson B. (1995) Prolongation of inhibitory postsynaptic currents by pentobarbitone, halothane and ketamine in CA1 pyramidal cells in rat hippocampus.Br. J. Pharmacol. 85, 675–681.Google Scholar
  103. Gallagher J. P., Nakamura J. and Shinnick Gallagher P. (1983) The effects of temperature, pH and Cl-pump inhibitors on GABA responses recorded from cat dorsal root ganglia.Brain Res. 267, 249–259.PubMedCrossRefGoogle Scholar
  104. Gao B., Fritschy J. M., Benke D. and Mohler H. (1993) Neuron-specific expression of GABAA-receptor subtypes: differential association of the α1- and α3-subunits with serotonergic and GABAergic neurons.Neuroscience 54, 881–892.PubMedCrossRefGoogle Scholar
  105. Gao B., Hornung J. P. and Fritschy J. M. (1995) Identification of distinct GABAA-receptor subtypes in cholinergic and parvalbumin-positive neurons of the rat and marmoset medial septum-diagonal band complex.Neuroscience 65, 101–117.PubMedCrossRefGoogle Scholar
  106. Gee K. W. (1987) Phenylquinolines PK 8165 and PK 9084 allosterically modulate [35S]t-butylbicyclophosphorothionate binding to a chloride ionophore in rat brain via a novel Ro5-4864 binding site.J. Pharmacol. Exp. Ther. 240, 747–753.PubMedGoogle Scholar
  107. Gee K. W., Brinton R. E. and McEwen B. S. (1988) Regional distribution of a Ro5 4864 binding site that is functionally coupled to the γ-aminobutyric acid/benzodiazepine receptor complex in rat brain.J. Pharmacol. Exp. Ther. 244, 379–383.PubMedGoogle Scholar
  108. Gee, K. W. (1988) Steroid modulation of the GABA/benzodiazepine receptor-linked chloride ionophore.Mol. Neurobiol. 2, 291–317.PubMedGoogle Scholar
  109. Gee, K. W., Bolger, M. B., Brinton, R. E., Coirini, H. and McEwen, B. S. (1988) Steroid modulation of the chloride ionophore in rat brain: structure-activity requirements, regional dependence and mechanism of action.J. Pharmacol. Exp. Ther. 246, 803–812.PubMedGoogle Scholar
  110. Gingrich K. J., Roberts W. A. and Kass R. S. (1995) Dependence of the GABAA receptor gating kinetics on the α-subunit isoform: implications for structure-function relations and synaptic transmission.J. Physiol Lond 489, 529–543.PubMedGoogle Scholar
  111. Glass M. and Dragunow M. (1995) Neurochemical and morphological changes associated with human epilepsy.Brain Res. Rev. 21, 29–41.PubMedCrossRefGoogle Scholar
  112. Granger P., Biton B., Faure C., Vige X., Depoortere H., et al. (1995) Modulation of the γ-aminobutyric acid type A receptor by the antiepileptic drugs carbamazepine and phenytoin.Mol. Pharmacol. 47, 1189–1196.PubMedGoogle Scholar
  113. Gray R. and Johnston D. (1985) Rectification of single GABA-gated chloride channels in adult hippocampal neurons.J. Neurophysiol. 54, 134–142.PubMedGoogle Scholar
  114. Greger R. and Wangemann P. (1987) Loop diuretics.Renal Physiol. 10, 174–183.PubMedGoogle Scholar
  115. Gunther U., Benson J., Benke D., Fritschy J. M., Reyes G. et al. (1995) Benzodiazepine-insensitive mice generated by targeted disruption of the γ2 subunit gene of γ-aminobutyric acid type A receptors.Proc. Natl. Acad. Sci. USA 92, 7749–7753.PubMedCrossRefGoogle Scholar
  116. Gurley D., Amin J., Ross P. C., Weiss D. S. and White G. (1995) Point mutations in the M2 region of the α, β, or γ subunit of the GABAA channel that abolish block by picrotoxin.Rec. Channels 3, 13–20.Google Scholar
  117. Gutierrez A., Khan Z. U. and De Blas A. L. (1994) Immunocytochemical localization of γ2 short and γ2 long subunits of the GABAA receptor in the rat brain.J. Neurosci. 14, 7168–7179.PubMedGoogle Scholar
  118. Gutierrez A., Khan Z. U. and DeBlas, A. L. (1996) Immunocytochemical localization of the α(6) subunit of the γ-aminobutyric AcidA receptor in the rat nervous system.J. Comp. Neurol. 365, 504–510.PubMedCrossRefGoogle Scholar
  119. Hadingham K. L., Wafford K. A., Thompson S. A., Palmer K. J. and Whiting P. J. (1995) Expression and pharmacology of human GABAA receptors containing γ3 subunits.Eur. J. Pharmacol.-Molec. Pharm. 291, 301–309.CrossRefGoogle Scholar
  120. Hadingham K. L., Wingrove P. B., Wafford K. A., Bain C., Kemp J. A. et al. (1993) Role of the β subunit in determining the pharmacology of human γ-aminobutyric acid type A receptors [published erratum appears inMol. Pharmacol. 1994 Jul;46(1):211].Mol. Pharmacol. 44, 1211–1218.PubMedGoogle Scholar
  121. Hadingham K. L., Wingrove P., Le Bourdelles B., Palmer K. J., Ragan C. I. and Whiting P. J. (1993) Cloning of cDNA sequences encoding human α2 and α3 γ-aminobutyric acidA receptor subunits and characterization of the benzodiazepine pharmacology of recombinant α1-, α2-, α3-, and α5-containing human γ-aminobutyric acidA receptors.Mol. Pharmacol. 43, 970–975.PubMedGoogle Scholar
  122. Haefely, W. (1985) Pharmacology of benzodiazepine antagonists.Pharmacopsychiatry 18, 163–166.PubMedGoogle Scholar
  123. Halasy K. and Somogyi P. (1993) Distribution of GABAergic synapses and their targets in the dentate gyrus of rat: a quantitative immunoelectron microscopic analysis.J. Hirnforsch. 34, 299–308.PubMedGoogle Scholar
  124. Hales T. G. and Lambert J. J. (1991) The actions of propofol on inhibitory amino acid receptors of bovine adrenomedullary chromaffin cells and rodent central neurones.Br. J. Pharmacol. 104, 619–628.PubMedGoogle Scholar
  125. Hales, T. G. and Tyndale, R. F. (1994) Few cell lines with GABAA mRNAs have functional receptors.J. Neurosci. 14, 5429–5436.PubMedGoogle Scholar
  126. Hall A. C., Lieb W. R. and Franks N. P. (1994) Stereoselective and non-stereoselective actions of isoflurane on the GABAA receptor.Br. J. Pharmacol. 112, 906–910.PubMedGoogle Scholar
  127. Hamann M., Desarmenien M., Vanderheyden P., Piguet P. and Feltz P. (1990) Electrophysiological study of tert-butylbicyclophosphorothionate-induced block of spontaneous chloride channels.Mol. Pharmacol. 37, 578–582.PubMedGoogle Scholar
  128. Harris B. D., Moody E. J., Gu Z. Q. and Skolnick P. (1995) Contribution of “diazepam-insensitive” GABAA receptors to the alcohol antagonist properties of ro 15-4513 and related imidazobenzodiazepines.Pharmacol. Biochem. Behav. 52, 113–118.PubMedCrossRefGoogle Scholar
  129. Harris B., Wong G. and Skolnick P. (1993) Neurochemical actions of inhalational anesthetics at the GABAA receptor complex.J. Pharmacol. Exp. Ther. 265, 1392–1398.PubMedGoogle Scholar
  130. Harris R. A., McQuilkin S. J., Paylor R., Abeliovich A., Tonegawa S. and Wehner J. M. (1995) Mutant mice lacking the γ isoform of protein kinase C show decreased behavioral actions of ethanol and altered function of γ-aminobutyrate type A receptors [see comments].Proc. Natl. Acad. Sci. USA 92, 3658–3662.PubMedCrossRefGoogle Scholar
  131. Harris R. A., Mihic S. J., Dildymayfield J. E. and Machu T. K. (1995) Actions of anethetics on ligand-gated ion channels: Role of receptor subunit composition.FASEB J. 9, 1454–1462.PubMedGoogle Scholar
  132. Harris R. A., Proctor W. R., McQuilkin S. J., Klein R. L., Mascia M. P., et al. (1995) Ethanol increases GABAA responses in cells stably transfected with receptor subunits.Alcohol. Clin. Exp. Res. 19, 226–232.PubMedCrossRefGoogle Scholar
  133. Harrison N. L., Kugler J. L., Jones M. V., Greenblatt E. P. and Pritchett D. B. (1993) Positive modulation of human γ-aminobutyric acid type A and glycine receptors by the inhalation anesthetic isoflurane.Mol. Pharmacol. 44, 628–632.PubMedGoogle Scholar
  134. Harrison, N. L. and Simmonds, M. A. (1984) Modulation of the GABA receptor complex by a steroid anaesthetic.Brain Res. 323, 287–292.PubMedCrossRefGoogle Scholar
  135. Harrison, N. L., Majewska, M. D., Harrington, J. W. and Barker, J. L. (1987) Structure-activity relationships for steroid interaction with the γ-aminobutyric acidA receptor complex.J. Pharmacol. Exp. Ther. 241, 346–353.PubMedGoogle Scholar
  136. Harrison, N. L., Vicini, S. and Barker, J. L. (1987) A steroid anesthetic prolongs inhibitory postsynaptic currents in cultured rat hippocampal neurons.J. Neurosci. 7, 604–609.PubMedGoogle Scholar
  137. Harvey, R. J., Chinchetru, M. A. and Darlison M. G. (1994) Alternative splicing of a 51-nucleotide exon that encodes a putative protein kinase C phosphorylation site generates two forms of the chicken γ-aminobutyric acidA receptor β2 subunit.J. Neurochem. 62, 10–16.PubMedCrossRefGoogle Scholar
  138. Hattori, K., Akaike, N., Oomura, Y. and Kuraoka, S. (1984) Internal perfusion studies demonstrating GABA-induced chloride responses in frog primary afferent neurons.Am. J. Physiol. 246, C259–265.PubMedGoogle Scholar
  139. Hattori, K., Oomura, Y. and Akaike, N. (1986) Diazepam action on γ-aminobutyric acid-activated chloride currents in internally perfused frog sensory neurons.Cell. Mol. Neurobiol. 6, 307–323.PubMedCrossRefGoogle Scholar
  140. Hauser C. A., Chesnoy Marchais D., Robel P. and Baulieu E. E. (1995) Modulation of recombinant α 6β2γ2 GABAA receptors by neuroactive steroids.Eur. J. Pharmacol. 289, 249–257.PubMedCrossRefGoogle Scholar
  141. Heaulme, M., Chambon J. P., Leyris, R., Wermuth, C. G. and Biziere, K. (1987) Characterization of the binding of [3H]SR 95531, a GABAA antagonist, to rat brain membranes.J. Neurochem. 48, 1677–1686.PubMedCrossRefGoogle Scholar
  142. Herb, A., Wisden, W., Lüddens, H., Puia, G., Vicini, S. and Seeburg, P. H. (1992) The third γ subunit of the γ-aminobutyric acid type A receptor family.Proc. Natl. Acad. Sci. USA 89, 1433–1437.PubMedCrossRefGoogle Scholar
  143. Herblin W. F. and Mechem C. C. (1984) Short-wave ultraviolet irradiation increases photo-affinity labeling of benzodiazepine sites.Life Sci. 35, 317–324.PubMedCrossRefGoogle Scholar
  144. Horne A. L., Harkness P. C., Hadingham K. L., Whitting P. and Kemp J. A. (1993) The influence of the γ2L subunit on the modulation of responses to GABAA receptor activation.Br. J. Pharmacol. 108, 711–716.PubMedGoogle Scholar
  145. Hunt, P. and Clements Jewery, S. (1981) A steroid derivative, R 5135, antagonizes the GABA/benzodiazepine receptor interaction.Neuropharmacology 20, 357–361.PubMedCrossRefGoogle Scholar
  146. Im H. K., Im W. B., Hamilton B. J., Carter D. B. and Vonvoigtlander P. F. (1993) Potentiation of γ-aminobutyric acid-induced chloride currents by various benzodiazepine site agonists with the α1γ2, β2γ2 and α1β2γ2 subtypes of cloned γ-aminobutyric acid type A receptors.Mol. Pharmacol. 44, 866–870.PubMedGoogle Scholar
  147. Im H. K., Im, W. B., Carter D. B. and McKinley D. D. (1995) Interaction of β-carboline inverse agonists for the benzodiazepine site with another site on GABAA receptors.Br. J. Pharmacol. 114, 1040–1044.PubMedGoogle Scholar
  148. Im M. S., Hamilton B. J., Carter D. B. and Im W. B. (1992) Selective potentiation of GABA-mediated Cl current by lanthanum ion in subtypes of cloned GABAA receptors.Neurosci. Lett. 144, 165–168.PubMedCrossRefGoogle Scholar
  149. Im W. B. and Blakeman D. P. (1991) Correlation between γ-aminobutyric acidA receptor ligand-induced changes in t-butylbicyclophosphoro[35S] thionate binding and36CI- uptake in rat cerebrocortical membranes.Mol. Pharmacol. 39, 394–398.PubMedGoogle Scholar
  150. Im W. B., Im H. K., Pregenzer J. F., Hamilton B. J., Carter D. B. et al. (1993) Differential affinity of dihydroimidazoquinoxalines and diimidazoquinazolines to the α1β2γ2 and α6β2γ2 subtypes of cloned GABAA receptors.Br. J. Pharmacol. 110, 677–680.PubMedGoogle Scholar
  151. Im, W. B., Blakeman, D. P., Davis, J. P. and Ayer D. E. (1990) Studies on the mechanism of interactions between anesthetic steroids and γ-aminobutyric acidA receptors.Mol. Pharmacol. 37, 429–434.PubMedGoogle Scholar
  152. Inomata N., Ishihara T. and Akaike N. (1988) Effects of diuretics on GABA-gated chloride current in frog isolated sensory neurones.Br. J. Pharmacol. 93, 679–683.PubMedGoogle Scholar
  153. Inomata N., Tokutomi N., Oyama Y. and Akaike N. (1988) Intracellular picrotoxin blocks pentobarbital-gated Cl- conductance.Neurosci. Res. 6, 72–75.PubMedCrossRefGoogle Scholar
  154. Inoue M. and Akaike N. (1988) Blockade of γ-aminobutyric acid-gated chloride current in frog sensory neurons by picrotoxin.Neurosci. Res. 5 380–394.PubMedCrossRefGoogle Scholar
  155. Jackson M. B., Lecar H., Mathers D. A. and Barker J. L. (1982) Single channel currents activated by γ-aminobutyric acid, muscimol, and (−)-pentobarbital in cultured mouse spinal neurons.J. Neurosci. 2, 889–894.PubMedGoogle Scholar
  156. Johnston, G. A., Curtis, D. R., Beart, P. M., Game C. J., McCulloch, R. M. and Twitchin, B. (1975) Cis-and trans-4-aminocrotonic acid as GABA analogues of restricted conformation.J. Neurochem. 24, 157–160.PubMedCrossRefGoogle Scholar
  157. Jones M. V. and Harrison N. L. (1993) Effects of volatile anesthetics on the kinetics of inhibitory postsynaptic currents in cultured rat hippocampal neurons.J. Neurophysiol. 70, 1339–1349.PubMedGoogle Scholar
  158. Jones M. V. and Westbrook G. L. (1995) Desensitized states prolong GABAA channel responses to brief agonist pulses.Neuron 15, 181–191.PubMedCrossRefGoogle Scholar
  159. Jones M. V., Harrison N. L., Pritchett D. B. and Hales T. G. (1995) Modulation of the GABAA receptor by propofol is independent of the γ subunit.J. Pharmacol. Exper. Therap. 274, 962–968.Google Scholar
  160. Jones, A., Korpi, E. R., McKernan, R. M., Nusser, A., Pelz R. et al. (1997) Ligand-gated ion channel subunit partnerships: GABAA receptor γ6 subunit gene inactivation inhibits δ subunit expression.J. Neurosci. (Submitted)Google Scholar
  161. Joyce K. A., Atkinson A. E., Bermudez I., Beadle D. J. and King L. A. (1993) Synthesis of functional GABAA receptors in stable insect cell lines.FEBS Lett. 335, 61–64.PubMedCrossRefGoogle Scholar
  162. Kardos, J. and Cash, D. J. (1990) Transmembrane 36Cl-flux measurements and desensitization of the γ-aminobutyric acidA receptor.J. Neurochem. 55, 1095–1099.PubMedCrossRefGoogle Scholar
  163. Karlin A. and Akabas M. H., (1995) Toward a structural basis for the function of nicotinic acetylcholine receptors and their cousins.Neuron 15, 1231–1244.PubMedCrossRefGoogle Scholar
  164. Karobath M., Drexler G. and Supavilai P. (1981) Modulation by picrotoxin and IPTBO of3H-flunitrazepam binding to the GABA/benzodiazepine receptor complex of rat cerebellum.Life Sci. 28, 307–313.PubMedCrossRefGoogle Scholar
  165. Karobath, M. and Sperk, G. (1979) Stimulation of benzodiazepine receptor binding by γ-aminobutyric acid.Proc. Natl. Acad. Sci. USA 76, 1004–1006.PubMedCrossRefGoogle Scholar
  166. Kato K. (1990) Novel GABAA receptor α subunit is expressed only in cerebellar granule cells.J. Mol. Biol. 214, 619–624.PubMedCrossRefGoogle Scholar
  167. Kaupmann K., Huggel K., Heid J., Flor P. J., Bischoff S. et al. (1997) Expression cloning of GABAB receptors uncovers similarity to metabotropic glutamate receptors.Nature 386, 239–246.PubMedCrossRefGoogle Scholar
  168. Kerr D. I. B. and Ong J. (1995) GABAB receptors.Pharmacol. Ther. 67, 187–246.PubMedCrossRefGoogle Scholar
  169. Khan Z. U., Gutierrez A. and De Blas A. L. (1994) The subunit composition of a GABAA benzodiazepine receptor from rat cerebellum.J. Neurochem. 63, 371–374.PubMedCrossRefGoogle Scholar
  170. Khrestchatisky M., MacLennan A. J., Chiang M. Y., Xu W. T., Jackson M. B., et al. (1989) A novel α subunit in rat brain GABAA receptors.Neuron 3, 745–753.PubMedCrossRefGoogle Scholar
  171. Kirkness, E. F. and Fraser, C. M. (1993) A strong promoter element is located between alternative exons of a gene encoding the human γ-aminobutyric acid-type A receptor β3 subunit (GABRB3).J. Biol. Chem. 268, 4420–4428.PubMedGoogle Scholar
  172. Kleingoor, C., Ewert M., von Blankenfeld G., Seeburg P. H. and Kettenmann H. (1991) Inverse but not full benzodiazepine agonists modulate recombinant α6 β2 γ2 GABAA receptors in transfected human embryonic kidney cells.Neurosci. Lett. 130, 169–172.PubMedCrossRefGoogle Scholar
  173. Kleingoor C., Wieland H. A., Korpi E. R., Seeburg P. H. and Kettenmann H. (1993) Current potentiation by diazepam but not GABA sensitivity is determined by a single histidine residue.Neuroreport 4, 187–190.PubMedCrossRefGoogle Scholar
  174. Knoflach, F., Benke D., et al. (1996) Pharmacological modulation of the diazepam-insensitive recombinant γ-aminobutyric acidA receptors α4 β2 γ2 and α6 β2 γ2.Mol. Pharmacol. 50, 1253–1261.PubMedGoogle Scholar
  175. Knoflach, F., Drescher, U., Scheurer, L., Malherbe, P. and Mohler, H. (1993) Full and partial agonism displayed by benzodiazepine receptor ligands at recombinant γ-aminobutyric acidA receptor subtypes.J. Pharmacol. Exp. Ther. 266, 385–391.PubMedGoogle Scholar
  176. Knoflach, F., Rhyner, T., Villa, M., Kellenberger, S., Drescher, U., et al. (1991) The γ3-subunit of the GABAA receptor confers sensitivity to benzodiazepine receptor ligands.FEBS Lett. 293, 191–194.PubMedCrossRefGoogle Scholar
  177. Kofuji, P., Wang, J. B., Moss, S. J., Huganir, R. L. and Burt, D. R. (1991) Generation of two forms of the γ- aminobutyric acidA receptor γ2-subunit in mice by alternative splicing.J. Neurochem. 56, 713–715.PubMedCrossRefGoogle Scholar
  178. Kokate, T. G., Svensson, B. E. and Rogawski, M. A. (1994) Anticonvulsant activity of neurosteroids: correlation with γ-aminobutyric acid-evoked chloride current potentiation.J. Pharmacol. Exp. Ther. 270, 1223–1229.PubMedGoogle Scholar
  179. Korpi E. R. (1994) Role of GABAA receptors in the actions of alcohol and alcoholism: recent advances.Alcohol. Alcoholism 29, 115–129.Google Scholar
  180. Korpi E. R. and Lüddens H. (1993) Regional γ-aminobutyric acid sensitivity of t-butylbicyclophosphoro [35S]thionate binding depends on γ-aminobutyric acidA receptor α subunit.Mol. Pharmacol. 44, 87–92.PubMedGoogle Scholar
  181. Korpi E. R. and Lüddens H. (1997) Furosemide interactions with brain GABAA receptors.Br. J. Pharmacol. 120, 741–748.PubMedCrossRefGoogle Scholar
  182. Korpi E. R., Kleingoor C., Kettenmann H. and Seeburg P. H. (1993) Benzodiazepine-induced motor impairment linked to point mutation in cerebellar GABAA receptor.Nature 361, 356–359.PubMedCrossRefGoogle Scholar
  183. Korpi E. R., Kuner T., Seeburg P. H., and Lüddens H. (1995) Selective antagonist for the cerebellar granule cell-specific γ-aminobutyric acid type A receptor.Mol. Pharmacol. 47, 283–289.PubMedGoogle Scholar
  184. Korpi, E. R., Kuner, T., Kristo, P., Köhler, M., Herb, A., Lüddens, H. and Seeburg, P. H. (1994) Small N-terminal deletion by splicing in cerebellar α6 subunit abolishes GABAA receptor function.J. Neurochem. 63, 1167–1170.PubMedCrossRefGoogle Scholar
  185. Krishek B. J., Moss S. J. and Smart T. G. (1996) Homomeric β 1 γ-aminobutyric acidA receptorion channels: evaluation of pharmacological and physiological properties.Mol. Pharmacol. 49, 494–504.PubMedGoogle Scholar
  186. Krogsgaard Larsen, P., Frolund, B., Jorgensen, F. S. and Schousboe, A. (1994) GABAA receptor agonists, partial agonists, and antagonists. Design and therapeutic prospects.J. Med. Chem. 37, 2489–2505.PubMedCrossRefGoogle Scholar
  187. Kusama T., Spivak C. E., Whiting P., Dawson V. L., Schaeffer J. C. and Uhl G. R. (1993a) Pharmacology of GABA ρ1 and GABA α/β receptors expressed inXenopus oocytes and COS cells.Br. J. Pharmacol. 109, 200–206.PubMedGoogle Scholar
  188. Kusama T., Wang T. L., Guggino W. B., Cutting G. R. and Uhl G. R. (1993b) GABA ρ2 receptor pharmacological profile: GABA recognition site similarities to ρ1.Eur. J. Pharmacol. 245, 83–84.PubMedCrossRefGoogle Scholar
  189. Lüddens H. and Korpi E. (1996) GABAA receptors: pharmacology, behavioral, roles and motor disorders.Neuroscientist 2, 15–23.Google Scholar
  190. Lüddens H. and Korpi E. R. (1995) GABA antagonists differentiate between recombinant GABAA/benzodiazepine receptor subtypes.J. Neurosci. 15, 6957–6962.PubMedGoogle Scholar
  191. Lüddens H. and Wisden W. (1991) Function and pharmacology of multiple GABAA receptor subunits.Trends Pharmacol. Sci. 12, 49–51.PubMedCrossRefGoogle Scholar
  192. Lüddens H., Seeburg P. H. and Korpi E. R. (1994) Impact of β and γ variants on ligand-binding properties of γ-aminobutyric acid type A receptors.Mol. Pharmacol. 45, 810–814.PubMedGoogle Scholar
  193. Lüddens, H., Pritchett D. B., Kohler, M., Killisch I., Keinanen, K. et al. (1990) Cerebellar GABAA receptor selective for a behavioural alcohol antagonist.Nature 346, 648–651.PubMedCrossRefGoogle Scholar
  194. Lambert J. J., Peters J. A., Sturgess N. C. and Hales T. G. (1990) Steroid modulation of the GABAA receptor complex: electrophysiology studies.Ciba Found. Symp. 153, 56–71.PubMedGoogle Scholar
  195. Laurie D. J., Seeburg P. H. and Wisden W. (1992) The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. II. Olfactory Bulb and Cerebellum.J. Neurosci. 12, 1063–1076.PubMedGoogle Scholar
  196. Laurie D. J., Wisden W. and Seeburg P. H. (1992) The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development.J. Neurosci. 12, 4151–4172.PubMedGoogle Scholar
  197. Lawrence L.J. and Casida J. E. (1984) Interactions of lindane, toxaphene and cyclodienes with brain-specific t-butylbicyclophosphorothionate receptor.Life Sci. 35, 171–178.PubMedCrossRefGoogle Scholar
  198. Leeb Lundberg F., Snowman A. and Olsen R. W. (1980) Barbiturate receptor sites are coupled to benzodiazepine receptors.Proc. Natl. Acad. Sci. USA 77, 7468–7472.PubMedCrossRefGoogle Scholar
  199. Leeb Lundberg F., Snowman A. and Olsen R. W. (1981) Interaction of anticonvulsants with the barbiturate-benzodiazepine-GABA receptor complex.Eur. J. Pharmacol. 72, 125–129.PubMedCrossRefGoogle Scholar
  200. Leeb Lundberg F., Snowman A., and Olsen R. W. (1981) Perturbation of benzodiazepine receptor binding by pyrazolopyridines involves picrotoxinin/barbiturate receptor sites.J. Neurosci. 1, 471–477.PubMedGoogle Scholar
  201. Leidenheimer, N. J., Browning, M. D. and Harris, R. A. (1991) GABAA receptor phosphorylation: multiple sites, actions and artifacts.Trends Pharmacol. Sci. 12, 84–87.PubMedCrossRefGoogle Scholar
  202. Levitan E. S., Blair L. A., Dionne V. E. and Barnard, E. A. (1988) Biophysical and pharmacological properties of cloned GABAA receptor subunits expressed inXenopus oocytes.Neuron 1, 773–781.PubMedCrossRefGoogle Scholar
  203. Levitan E. S., Schofield P. R., Burt D. R., Rhee L. M., Wisden W. et al. (1988) Structural and functional basis for GABAA receptor heterogeneity.Nature 335, 76–79.PubMedCrossRefGoogle Scholar
  204. Lin A. M., Bickford P. C. and Palmer M. R. (1993) The effects of ethanol on γ-aminobutyric acid-induced depressions of cerebellar Purkinje neurons: influence of β adrenergic receptor action in young and aged Fischer 344 rats.J. Pharmacol. Exp. Ther. 264, 951–957.PubMedGoogle Scholar
  205. Lin A. M., Freund R. K. and Palmer M. R. (1993) Sensitization of γ-aminobutyric acid-induced depression of cerebellar Purkinje neurons to the potentiative effects of ethanol by β adrenergic mechanisms in rat brain.J. Pharmacol. Exp. Ther. 265, 426–432.PubMedGoogle Scholar
  206. Lin L. H., Chen L. L., Zirrolli J. A. and Harris R. A. (1992) General anesthetics potentiate γ-aminobutyric acid actions on γ-aminobutyric acidA receptors expressed byXenopus oocytes: lack of involvement of intracellular calcium.J. Pharmacol. Exp. Ther. 263, 569–578.PubMedGoogle Scholar
  207. Lin Y. F., Angelotti T. P., Dudek E. M., Browning M. D. and Macdonald R. L. (1996) Enhancement of recombinant α1β1γ2L γ-aminobutyric acidA receptor whole-cell currents by protein kinase C is mediated through phosphorylation of both β1 and γ2L subunits.Mol. Pharmacol. 50, 185–195.PubMedGoogle Scholar
  208. Liu D. T., Tibbs G. R. and Siegelbaum S. A. (1996) Subunit stoichiometry of cyclic nucleotide-gated channels and effects of subunit order on channel function.Neuron 16, 983–990.PubMedCrossRefGoogle Scholar
  209. Liu R., Hu R. J., Zhang P., Skolnick P. and Cook J. M. (1996) Synthesis and pharmacological properties of novel 8-substituted imidazobenzodiazepines: high-affinity, selective probes for α 5-containing GABAA receptors.J Med Chem 39, 1928–1934.PubMedCrossRefGoogle Scholar
  210. Lloyd, G. K., Danielou, G. and Thuret, F. (1990) The activity of zolpidem and other hypnotics within the γ-aminobutyric acid (GABAA) receptor supramolecular complex, as determined by35S-t-butylbicyclophosphorothionate (35S-TBPS) binding to rat cerebral cortex membranes.J. Pharmacol. Exp. Ther. 255, 690–696.PubMedGoogle Scholar
  211. Lo M. M., Strittmatter S. M. and Snyder S. H. (1982) Physical separation and characterization of two types of benzodiazepine receptors.Proc. Natl. Acad. Sci. USA 79, 680–684.PubMedCrossRefGoogle Scholar
  212. Lolait, S. J., AM, O. C., Kusano, K. and Mahan, L. C. (1989) Pharmacological characterization and region-specific expression in brain of the β2- and β-3-subunits of the rat GABAA receptor.FEBS Lett. 258, 17–21.PubMedCrossRefGoogle Scholar
  213. Longoni B. and Olsen R. W. (1992) Studies on the mechanism of interaction of anesthetics with GABA-A receptors.Adv. Biochem. Psychopharmacol. 47, 365–378.PubMedGoogle Scholar
  214. Longoni B., Demontis G. C. and Olsen R. W. (1993) Enhancement of γ-aminobutyric acidA receptor function and binding by the volatile anesthetic halothane.J. Pharmacol. Exp. Ther. 266, 153–159.PubMedGoogle Scholar
  215. Möhler H., Malherbe P., Draguhn A. and Richards J. G. (1990) GABAA-receptors: structural requirements and sites of gene expression in mammalian brain.Neurochem. Res. 15, 199–207.PubMedCrossRefGoogle Scholar
  216. Macdonald R. L. (1995) Ethanol, γ-aminobutyrate type A receptors, and protein kinase C phosphorylation [comment].Proc. Natl. Acad. Sci. USA 92, 3633–3635.PubMedCrossRefGoogle Scholar
  217. Macdonald R. L. and Barker J. L. (1978) Different actions of anticonvulsant and anesthetic barbiturates revealed by use of cultured mammalian neurons.Science 200, 775–777.PubMedCrossRefGoogle Scholar
  218. Macdonald R. L. and Olsen R. W. (1994) GABAA receptor channels.Annu. Rev. Neurosci. 17, 569–602.PubMedGoogle Scholar
  219. Macdonald R. L. and Twyman R. E. (1992) Kinetic properties and regulation of GABAA receptor channels.Ion Channels 3, 315–343.PubMedGoogle Scholar
  220. Macdonald R. L., Rogers C. J. and Twyman R. E. (1989) Barbiturate regulation of kinetic properties of the GABAA receptor channel of mouse spinal neurones in culture.J. Physiol. Lond. 417, 483–500.PubMedGoogle Scholar
  221. Macdonald R. L., Rogers C. J. and Twyman R. E. (1989) Kinetic properties of the GABAA receptor main conductance state of mouse spinal cord neurones in culture.J. Physiol. Lond. 410, 479–499.PubMedGoogle Scholar
  222. Macdonald R. L., Twyman, R. E., Ryan Jastrow, T. and Angelotti, T. P. (1992) Regulation of GABAA receptor channels by anticonvulsant and convulsant drugs and by phosphorylation.Epilepsy Res. Suppl. 9, 265–277.PubMedGoogle Scholar
  223. Macdonald, R. and Barker, J. L. (1978) Benzodiazepines specifically modulate GABA-mediated postsynaptic inhibition in cultured mammalian neurones.Nature 271, 563–564.PubMedCrossRefGoogle Scholar
  224. MacIver M. B., Tanelian D. L. and Mody I. (1991) Two mechanisms for anesthetic-induced enhancement of GABAA-mediated neuronal inhibition.Ann. NY Acad. Sci. 625, 91–96.PubMedCrossRefGoogle Scholar
  225. Maconochie, D. J., Zempel, J. M. and Steinbach, J. H. (1994) How quickly can GABAA receptors open?Neuron 12, 61–71.PubMedCrossRefGoogle Scholar
  226. Majewska M. D. (1988) Interaction of ethanol with the GABAA receptor in the rat brain: possible involvement of endogenous steroids.Alcohol 5, 269–273.PubMedCrossRefGoogle Scholar
  227. Majewska M. D. and Schwartz R. D. (1987) Pregnenolone-sulfate: an endogenous antagonist of the γ-aminobutyric acid receptor complex in brain?Brain Res. 404, 355–360.PubMedCrossRefGoogle Scholar
  228. Majewska M. D., Bisserbe J. C. and Eskay R. L. (1985) Glucocorticoids are modulators of GABAA receptors in brain.Brain Res. 339, 178–182.PubMedCrossRefGoogle Scholar
  229. Majewska M. D., Mienville J. M. and Vicini S. (1988) Neurosteroid pregnenolone sulfate antagonizes electrophysiological responses to GABA in neurons.Neurosci. Lett. 90, 279–284.PubMedCrossRefGoogle Scholar
  230. Majewska, M. D. (1992) Neurosteroids: endogenous bimodal modulators of the GABAA receptor. Mechanism of action and physiological significance.Prog. Neurobiol. 38, 379–395.PubMedCrossRefGoogle Scholar
  231. Majewska, M. D., Harrison, N. L., Schwartz, R. D., Barker, J. L. and Paul, S. M. (1986) Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor.Science 232, 1004–1007.PubMedCrossRefGoogle Scholar
  232. Maksay G. (1994) Thermodynamics of γ-aminobutyric acid type A receptor binding differentiate agonists from antagonists.Mol. Pharmacol. 46, 386–390.PubMedGoogle Scholar
  233. Maksay G. and Simonyi M. (1985) Benzodiazepine anticonvulsants accelerate and β-carboline convulsants decelerate the kinetics of [35S]TBPS binding at the chloride ionophore.Eur. J. Pharmacol. 117, 275–278.PubMedCrossRefGoogle Scholar
  234. Maksay G. and Simonyi M. (1986) Kinetic regulation of convulsant (TBPS) binding by GABAergic agents.Mol. Pharmacol. 30, 321–328.PubMedGoogle Scholar
  235. Maksay G. and Simonyi M. (1988) Nonequilibrium modulation of [35S]-TBPS binding by benzodiazepine agonists and antagonists.Biochem. Pharmacol. 37, 2195–2200.PubMedCrossRefGoogle Scholar
  236. Maksay G. and Ticku M. K. (1985) GABA, depressants and chloride ions affect the rate of dissociation of [35S]-t-butylbicyclophosphorothionate binding.Life Sci. 37, 2173–2180.PubMedCrossRefGoogle Scholar
  237. Maksay G. and van Rijn C. M. (1993) Interconvertible kinetic states of t-butylbicycloorthobenzoate binding sites of the γ-aminobutyric acidA ionophores.J. Neurochem. 61, 2081–2088.PubMedCrossRefGoogle Scholar
  238. Malatynska E., Giroux M. L., Dilsaver S. C. and Schwarzkopf S. B. (1992) Bidirectional effect of β-carboline agonists at the benzodiazepine-GABAA receptor chloride ionophore complex on GABA-stimulated36CI-uptake.Brain Res. Bull. 28, 605–611.PubMedCrossRefGoogle Scholar
  239. Malherbe P., Draguhn A., Multhaup G., Beyreuther K. and Möhler H. (1990) GABAA-receptor expressed from rat brain α- and β-subunit cDNAs displays potentiation by benzodiazepine receptor ligands.Mol. Brain Res. 8, 199–208.PubMedCrossRefGoogle Scholar
  240. Malherbe P., Sigel E., Baur R., Persohn E., Richards J. G. and Möhler H. (1990a) Functional characteristics and sites of gene expression of the α1, β1, γ2-isoform of the rat GABAA receptor.J. Neurosci. 10, 2330–2337.PubMedGoogle Scholar
  241. Malherbe P., Sigel E., Baur R., Persohn E., Richards J. G. and Möhler H. (1990b) Functional expression and sites of gene transcription of a novel α subunit of the GABAA receptor in rat brain.FEBS Lett. 260, 261–265.PubMedCrossRefGoogle Scholar
  242. Marszalec W., Kurata Y., Hamilton B. J., Carter D. B. and Narahashi T. (1994) Selective effects of alcohols on γ-aminobutyric acidA receptor subunits expressed in human embryonic kidney cells.J. Pharmacol. Exp. Ther. 269, 157–163.PubMedGoogle Scholar
  243. Martin I. L. and Doble A. (1983) The benzodiazepine receptor in rat brain and its interaction with ethyl β-carboline-3-carboxylate.J. Neurochem. 40, 1613–1619.PubMedCrossRefGoogle Scholar
  244. Martin J. V., Williams D. B., Fitzgerald R. M., Im H. K. and Vonvoigtlander P. F. (1996) Thyroid hormonal modulation of the binding and activity of the GABAA receptors complex of brain.Neuroscience 73, 705–713.PubMedCrossRefGoogle Scholar
  245. Mathers D. A. (1985) Spontaneous and GABA-induced single channel currents in cultured murine spinal cord neurons.Can. J. Physiol. Pharmacol. 63, 1228–1233.PubMedGoogle Scholar
  246. McEwen, B. S. and Parsons, B. (1982) Gonadal steroid action on the brain: neurochemistry and neuropharmacology.Annu. Rev. Pharmacol. Toxicol. 22, 555–598.PubMedCrossRefGoogle Scholar
  247. Mertens, S., Benke, D. and Mohler, H. (1993) GABAA receptor populations with novel subunit combinations and drug binding profiles identified in brain by α5- and δ-subunit-specific immunopurification.J. Biol. Chem. 268, 5965–5973.PubMedGoogle Scholar
  248. Mhatre M. C., Pena G., Sieghart W. and Ticku M. K. (1993) Antibodies specific for GABAA receptor α subunits reveal that chronic alcohol treatment down-regulates α-subunit expression in rat brain regions.J. Neurochem. 61, 1620–1625.PubMedCrossRefGoogle Scholar
  249. Michelson, H. B. and Wong, R. K. (1991) Excitatory synaptic responses mediated by GABAA receptors in the hippocampus.Science 253, 1420–1423.PubMedCrossRefGoogle Scholar
  250. Mienville J. M. and Vicini S. (1989) Pregnenolone sulfate antagonizes GABAA receptor-mediated currents via a reduction of channel opening frequency.Brain Res. 489, 190–194.PubMedCrossRefGoogle Scholar
  251. Mihic S. J., Sanna E., Whiting P. J. and Harris R. A. (1995) Pharmacology of recombinant GABAA receptors.GABA A Receptors and Anxiety48, 17–40.Google Scholar
  252. Mihic S. J., Whiting P. J. and Harris R. A. (1994) Anaesthetic concentrations of alcohols potentiate GABAA receptor-mediated currents: lack of subunit specificity.Eur. J. Pharmacol. 268, 209–214.PubMedCrossRefGoogle Scholar
  253. Mihic S. J., Whiting P. J., Klein R. L., Wafford K. A. and Harris R. A. (1994) A single amino acid of the human γ-aminobutyric acid type A receptor γ2 subunit determines benzodiazepine efficacy.J. Biol. Chem. 269, 32,768–32,773.Google Scholar
  254. Misgeld U., Bijak M. and Jarolimek W. (1995) A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system.Prog. Neurobiol. 46, 423–462.PubMedCrossRefGoogle Scholar
  255. Misgeld U., Deisz R. A., Dodt H. U. and Lux H. D. (1986) The role of chloride transport in postsynaptic inhibition of hippocampal neurons.Science 232, 1413–1415.PubMedCrossRefGoogle Scholar
  256. Mohler H., Burkard, W. P., Keller, H. H., Richards, J. G. and Haefely, W. (1981) Benzodiazepine antagonist Ro 15 1788: binding characteristics and interaction with drug-induced changes in dopamine turnover and cerebellar cGMP levels.J. Neurochem. 37, 714–722.PubMedCrossRefGoogle Scholar
  257. Mohler, H. and Okada, T. (1977) Properties of3H-diazepam binding to benzodiazepine receptors in rat cerebral cortex.Life Sci. 20, 2101–2110.PubMedCrossRefGoogle Scholar
  258. Morrow, A. L., Suzdak, P. D. and Paul, S. M. (1987) Steroid hormone metabolites potentiate GABA receptor-mediated chloride ion flux with nanomolar potency.Eur. J. Pharmacol. 142, 483–485.PubMedCrossRefGoogle Scholar
  259. Morrow, A. L., Suzdak, P. D. and Paul, S. M. (1988) Benzodiazepine, barbiturate, ethanol and hypnotic steroid hormone modulation of GABA-mediated chloride ion transport in rat brain synaptoneurosomes.Adv. Biochem. Psychopharmacol. 45, 247–261.PubMedGoogle Scholar
  260. Moss S. J., Ravindran A., Mei L., Wang J. B., Kofuji P., Huganir R. L. and Burt D. R. (1991) Characterization of recombinant GABAA receptors produced in transfected cells from murine α1, β1, and γ2 subunit cDNAs.Neurosci. Lett. 123, 265–268.PubMedCrossRefGoogle Scholar
  261. Moss S. J., Smart T. G., Porter N. M., Nayeem N., Devine J., et al. (1990) Cloned GABA receptors are maintained in a stable cell line: allosteric and channel properties.Eur. J. Pharmacol. 189, 77–88.PubMedCrossRefGoogle Scholar
  262. Moss, S. J., Gorrie, G. H., Amato, A. and Smart, T. G. (1995) Modulation of GABAA receptors by tyrosine phosphorylation.Nature 377, 344–348.PubMedCrossRefGoogle Scholar
  263. Nagata K. and Narahashi T. (1994) Dual action of the cyclodiene insecticide dieldrin on the γ-aminobutyric acid receptor-chloride channel complex of rat dorsal root ganglion neurons.J. Pharmacol. Exp. Ther. 269, 164–171.PubMedGoogle Scholar
  264. Nagata K., Hamilton B. J., Carter D. B. and Narahashi T. (1994) Selective effects of dieldrin on the GABAA receptor-channel subunits expressed in human embryonic kidney cells.Brain Res. 645, 19–26.PubMedCrossRefGoogle Scholar
  265. Nakahiro M., Yeh J. Z., Brunner E. and Narahashi T. (1989) General anesthetics modulate GABA receptor channel complex in rat dorsal root ganglion neurons.FASEB J. 3, 1850–1854.PubMedGoogle Scholar
  266. Nayeem N., Green T. P., Martin I. L. and Barnard E. A. (1994) Quaternary structure of the native GABAA receptor determined by electron microscopic image analysis.J. Neurochem. 62, 815–818.PubMedCrossRefGoogle Scholar
  267. Nevo I. and Hamon M. (1995) Neurotransmitter and neuromodulatory mechanisms involved in alcohol abuse and alcoholism.Neurochem. Int. 26, 305–336.PubMedCrossRefGoogle Scholar
  268. Newland C. F. and Cull C. S. (1992) On the mechanism of action of picrotoxin on GABA receptor channels in dissociated sympathetic neurones of the rat.J. Physiol. Lond. 447, 191–213.PubMedGoogle Scholar
  269. Nicoll R. A. (1978) The blockade of GABA mediated responses in the frog spinal cord by ammonium ions and furosemide.J. Physiol. Lond. 283, 121–132.PubMedGoogle Scholar
  270. Nielsen M. and Braestrup C. (1980) Ethyl-β-carboline-3-carboxylate shows differential benzodiazepine receptor interaction.Nature 286, 606–607.PubMedCrossRefGoogle Scholar
  271. Nistri, A. and Sivilotti, L. (1985) An unusual effect of γ-aminobutyric acid on synaptic transmission of frog tectal neurones in vitro.Br. J. Pharmacol. 85, 917–921.PubMedGoogle Scholar
  272. Nusser, Z., Sieghart, W., Stephenson, F. A. and Somogyi, P. (1996) The α6 subunit of the GABAA receptor is concentrated in both inhibitory and excitatory synapses on cerebellar granule cells.J. Neurosci. 16, 103–114.PubMedGoogle Scholar
  273. Nutt D. J. (1990) Pharmacological mechanisms of benzodiazepine withdrawal.J. Psychiatr. Res. 2, 105–110.CrossRefGoogle Scholar
  274. Nutt D. J. (1990) The pharmacology of human anxiety.Pharmacol. Ther. 47, 233–266.PubMedCrossRefGoogle Scholar
  275. Nutt, D. J., Smith, C. F., Bennett, R. and Jackson, H. C. (1992) Investigations on the “set-point” theory of benzodiazepine receptor function.Adv. Biochem. Psychopharmacol. 47, 419–429.PubMedGoogle Scholar
  276. Ogurusu T. and Shingai, R. (1996) Cloning of a putative γ-aminobutyric acid (GABA) receptor subunit rho 3 cDNA.Biochim. Biophys. Acta 1305, 15–18.PubMedGoogle Scholar
  277. Olsen R. W. and Snowman A. M. (1982) Chloride-dependent enhancement by barbiturates of γ-aminobutyric acid receptor binding.J. Neurosci. 2, 1812–1823.PubMedGoogle Scholar
  278. Olsen R. W. and Tobin A. J. (1990) Molecular biology of GABAA receptors.FASEB J. 4, 1469–1480.PubMedGoogle Scholar
  279. Olsen R. W., Bergman, M. O., Van Ness, P. C., Lummis, S. C., Watkins A. E., Napias, C. and Greenlee, D. V. (1981) γ-Aminobutyric acid receptor binding in mammalian brain. Heterogeneity of binding sites.Mol. Pharmacol. 19, 217–227.PubMedGoogle Scholar
  280. Olsen R. W., Yang J., King R. G., Dilber A., Stauber G. B. and Ransom R. W. (1986) Barbiturate and benzodiazepine modulation of GABA receptor binding and function.Life Sci. 39, 1969–1976.PubMedCrossRefGoogle Scholar
  281. Olsen, R. W. (1982) Drug interactions at the GABA receptor-ionophore complex.Annu. Rev. Pharmacol. Toxicol. 22, 245–277.PubMedCrossRefGoogle Scholar
  282. Olsen, R. W. and Snowman, A. M. (1983) [3H]bicuculline methochloride binding to low-affinity γ-aminobutyric acid receptor sites.J. Neurochem. 41, 1653–1663.PubMedCrossRefGoogle Scholar
  283. Ortells M. O. and Lunt G. G. (1995) Evolutionary history of the ligand-gated ion-channel super-family of receptors.Trends Neurosci. 18, 121–127.PubMedCrossRefGoogle Scholar
  284. Palmer M. R., van H. C., Harlan J. T. and Moore E. A. (1988) Antagonism of ethanol effects on cerebellar Purkinje neurons by the benzodiazepine inverse agonists Ro 15-4513 and FG 7142: electrophysiological studies.J. Pharmacol. Exp. Ther. 247, 1018–1024.PubMedGoogle Scholar
  285. Pearce R. A. (1993) Physiological evidence for two distinct GABAA responses in rat hippocampus.Neuron 10, 189–200.PubMedCrossRefGoogle Scholar
  286. Peduto V. A., Concas A., Santoro G., Biggio G. and Gessa G. L. (1991) Biochemical and electrophysiologic evidence that propofol enhances GABAergic transmission in the rat brain.Anesthesiology 75, 1000–1009.PubMedCrossRefGoogle Scholar
  287. Peters, J. A., Kirkness, E. F., Callachan H., Lambert, J. J. and Turner, A. J. (1988) Modulation of the GABAA receptor by depressant barbiturates and pregnane steroids.Br. J. Pharmacol. 94, 1257–1269.PubMedGoogle Scholar
  288. Petty F. (1995) GABA and mood disorders: a brief review and hypothesis.J. Affective Disord. 34, 275–281.CrossRefGoogle Scholar
  289. Polc, P. (1988) Electrophysiology of benzodiazepine receptor ligands: multiple mechanisms and sites of action.Prog. Neurobiol. 31, 349–423.PubMedCrossRefGoogle Scholar
  290. Polc, P., Bonetti, E. P., Schaffner, R. and Haefely, W. (1982) A three-state model of the benzodiazepine receptor explains the interactions between the benzodiazepine antagonist Ro 15-1788, benzodiazepine tranquilizers, β- carbolines, and phenobarbitone.Naunyn-Schmied. Arch. Pharmacol. 321, 260–264.CrossRefGoogle Scholar
  291. Pollard S., Duggan M. J. and Stephenson F. A. (1993) Further evidence for the existence of α subunit heterogeneity within discrete γ-aminobutyric acidA receptor subpopulations.J. Biol. Chem. 268, 3753–3757.PubMedGoogle Scholar
  292. Pollard, S., Thompson, C. L. and Stephenson F. A. (1995) Quantitative characterization of α6 and α1 α6 subunit-containing native γ-aminobutyric acidA receptors of adult rat cerebellum demonstrates two α subunits per receptor oligomer.J. Biol. Chem. 270, 21,285–21,290.Google Scholar
  293. Porter N. M., Angelotti T. P., Twyman R. E. and Macdonald R. L. (1992) Kinetic properties of α1β1 γ-aminobutyric acidA receptor channels expressed in Chinese hamster ovary cells: regulation by pentobarbital and picrotoxin.Mol. Pharmacol. 42, 872–881.PubMedGoogle Scholar
  294. Poulter M. O., Barker J. L., O'Carroll A. M., Lolait S. J. and Mahan L. C. (1992) Differential and transient expression of GABAA receptor α-subunit mRNAs in the developing rat CNS.J. Neurosci. 12, 2888–2900.PubMedGoogle Scholar
  295. Poulter M. O., Barker J. L., O'Carroll A. M., Lolait S. J. and Mahan L. C. (1993) Co-existent expression of GABAA receptor β2, β3 and γ2 subunit messenger RNAs during embryogenesis and early postnatal development of the rat central nervous system.Neuroscience 53, 1019–1033.PubMedCrossRefGoogle Scholar
  296. Pregenzer J. F., Im W. B., Carter D. B. and Thomsen D. R. (1993) Comparison of interactions of [3H]muscimol, t-butylbicyclophosphoro[35S]thionate, and [3H]flunitrazepam with cloned γ-aminobutyric acidA receptors of the α1β2 and α1β2γ2 subtypes.Mol. Pharmacol. 43, 801–806.PubMedGoogle Scholar
  297. Prinz, H. and Striessnig, J. (1993) Ligand-induced accelerated dissociation of (+)-cis-diltiazem from L-type Ca2+ channels is simply explained by competition for individual attachment points.J. Biol. Chem. 268, 18,580–18,585.Google Scholar
  298. Pritchett D. B. and Seeburg P. H. (1991) γ-Aminobutyric acid type A receptor point mutation increases the affinity of compounds for the benzodiazepine site.Proc. Natl. Acad. Sci. USA 88, 1421–1425.PubMedCrossRefGoogle Scholar
  299. Pritchett D. B., Lüddens H. and Seeburg P. H. (1989b) Type I and type II GABAA-benzodi-azepine receptors produced in transfected cells.Science 245, 1389–1392.PubMedCrossRefGoogle Scholar
  300. Pritchett D. B., Sontheimer H., Shivers B. D., Ymer S., Kettenmann H., Schofield P. R. and Seeburg P. H. (1989a) Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology.Nature 338, 582–585.PubMedCrossRefGoogle Scholar
  301. Pritchett, D. B. and Seeburg, P. H. (1990) γ-aminobutyric acidA receptor α5-subunit creates novel type II benzodiazepine receptor pharmacology.J. Neurochem. 54, 1802–1804.PubMedCrossRefGoogle Scholar
  302. Pritchett, D. B., Sontheimer, H., Gorman, C. M., Kettenmann, H., Seeburg, P. H. and Schofield P. R. (1988) Transient expression shows ligand gating and allosteric potentiation of GABAA receptor subunits.Science 242, 1306–1308.PubMedCrossRefGoogle Scholar
  303. Puia G., Ducic I., Vicini S. and Costa E. (1993) Does neurosteroid modulatory efficacy depend on GABAA receptor subunit composition?Rec. Channels 1, 135–142.Google Scholar
  304. Puia G., Santi M. R., Vicini S., Pritchett D. B., Purdy R. H., et al. (1990) Neurosteroids act on recombinant human GABAA receptors.Neuron 4, 759–765.PubMedCrossRefGoogle Scholar
  305. Puia G., Santi M. R., Vicini S., Pritchett D. B., Seeburg P. H. and Costa E. (1989) Differences in the negative allosteric modulation of γ-aminobutyric acid receptors elicited by 4′-chlorodiazepam and by a β-carboline-3-carboxylate ester: a study with natural and reconstituted receptors.Proc. Natl. Acad. Sci. USA 86, 7275–7279.PubMedCrossRefGoogle Scholar
  306. Puia, G., Ducic, I., Vicini, S. and Costa, E. (1992) Molecular mechanisms of the partial allosteric modulatory effects of bretazenil at γ-aminobutyric acid type A receptor.Proc. Natl. Acad. Sci. USA 89, 3620–3624.PubMedCrossRefGoogle Scholar
  307. Puia, G., Vicini, S., Seeburg, P. H. and Costa, E. (1991) Influence of recombinant γ-aminobutyric acid-A receptor subunit composition on the action of allosteric modulators of γ-aminobutyric acidgated Cl-currents.Mol. Pharmacol. 39, 691–696.PubMedGoogle Scholar
  308. Purdy R. H., Morrow A. L., Blinn J. R. and Paul S. M. (1990) Synthesis, metabolism and pharmacological activity of 3 alpha-hydroxy steroids which potentiate GABA-receptor-mediated chloride ion uptake in rat cerebral cortical synaptoneurosomes.J. Med. Chem. 33, 1572–1581.PubMedCrossRefGoogle Scholar
  309. Quirk K., Gillard N. P., Ragan C. I., Whiting P. J. and McKernan R. M. (1994) Model of subunit composition of γ-aminobutyric acidA receptor subtypes expressed in rat cerebellum with respect to their α and γ/δ subunits.J. Biol. Chem. 269, 16020–16028.PubMedGoogle Scholar
  310. Quirk, K., Gillard, N. P., Ragan, C. I., Whiting, P. J. and McKernan, R. M. (1994) γ-Aminobutyric acid type a receptors in the rat brain can contain both γ2 and γ3 subunits, but γ1 does not exist in combination with another γ subunit.Mol. Pharmacol. 45, 1061–1070.PubMedGoogle Scholar
  311. Rabow, L. E., Russek, S. J. and Farb, D. H. (1995) From ion currents to genomic analysis: recent advances in GABAA receptor research.Synapse 21, 189–274.PubMedCrossRefGoogle Scholar
  312. Ragan C. I., McKernan R. M., Wafford K. and Whiting P. J. (1993) γ-Aminobutyric acidA (GABAA) receptor/ion channel complex [published erratum appears inBiochem Soc. Trans. 1993 Nov;21(4):following 1201].Biochem. Soc. Trans. 21, 622–626.PubMedGoogle Scholar
  313. Rastogi S. K. and Ticku M. K. (1985) A possible role of a GABAergic mechanism in the convulsant action of RO5-4864.Pharmacol. Biochem. Behav. 23, 285–288.PubMedCrossRefGoogle Scholar
  314. Rogers C. J., Twyman R. E. and Macdonald R. L. (1994) Benzodiazepine and β-carboline regulation of single GABAA receptor channels of mouse spinal neurones in culture.J. Physiol. Lond. 475, 69–82.PubMedGoogle Scholar
  315. Rohrbough, J. and Spitzer, N. C. (1996) Regulation of intracellular Cl-levels by Na(+)-dependent Cl cotransport distinguishes depolarizing from hyperpolarizing GABAA receptor-mediated responses in spinal neurons.J. Neurosci. 16, 82–91.PubMedGoogle Scholar
  316. Rosenbaum J. F., Pollock R. A., Otto M. W. and Pollack M. H. (1995) Integrated treatment of panic disorder.Bull. Menninger. Clin. 59, A4–26.PubMedGoogle Scholar
  317. Rupprecht, R., Berning, B., Hauser, C. A. E., Holsboer, F. and Reul, J. M. H. M. (1996) Steroid receptor-mediated effects of neuroactive steroids: Characterization of structure-activity relationship.Eur. J. Pharmacol. 303, 227–234.PubMedCrossRefGoogle Scholar
  318. Sakmann B., Hamill O. P. and Bormann J. (1983) Patch-clamp measurements of elementary chloride currents activated by the putative inhibitory transmitter GABA and glycine in mammalian spinal neurons.J. Neural. Transm. Suppl. 18, 83–95.PubMedGoogle Scholar
  319. Sanna E. and Harris R. A. (1993) Recent developments in alcoholism: neuronal ion channels.Recent Dev. Alcohol. 11, 169–186.PubMedGoogle Scholar
  320. Sanna E., Garau F. and Harris R. A. (1995) Novel properties of homomeric β1 γ-aminobutyric acid type A receptors: actions of the anesthetics propofol and pentobarbital.Mol. Pharmacol. 47, 213–217.PubMedGoogle Scholar
  321. Saxena N. C. and Macdonald R. L. (1994) Assembly of GABAA receptor subunits—role of the δ-subunit.J. Neurosci. 14, 7077–7086.PubMedGoogle Scholar
  322. Saxena N. C. and Macdonald R. L. (1996) Properties of putative cerebellar γ-aminobutyric acidA receptor isoforms.Mol. Pharmacol. 49, 567–579.PubMedGoogle Scholar
  323. Schlatter E., Greger R. and Weidtke C. (1983) Effect of “high ceiling” diuretics on active salt transport in the cortical thick ascending limb of Henle's loop of rabbit kidney. Correlation of chemical structure and inhibitory potency.Pflügers. Arch. 396, 210–217.PubMedCrossRefGoogle Scholar
  324. Schofield P. R., Darlison M. G., Fujita N., Burt D. R., Stephenson F. A. et al. (1987) Sequence and functional expression of the GABAA receptor shows a ligand-gated receptor super-family.Nature 328, 221–227.PubMedCrossRefGoogle Scholar
  325. Seeburg P. H., Wisden W., Verdoorn T. A., Pritchett D. B., Werner P. et al. (1990) The GABAA receptor family—molecular and functional diversity.Cold Spring Harbor Symp. Quantit. Biol. 55, 29–40.Google Scholar
  326. Sequier J. M., Richards J. G., Malherbe P., Price G. W., Mathews S. and Möhler H. (1988) Mapping of brain areas containing RNA homologous to cDNAs encoding the α and β subunits of the rat GABAA γ-aminobutyrate receptor.Proc. Natl. Acad. Sci. USA 85, 7815–7819.PubMedCrossRefGoogle Scholar
  327. Serafini R., Valeyev, A. Y., Barker, J. L. and Poulter, M. O. (1995) Depolarizing GABA-activated Cl channels in embryonic rat spinal and olfactory bulb cells.J. Physiol. Lond. 488, 371–386.PubMedGoogle Scholar
  328. Shimada S., Cutting G. and Uhl G. R. (1992) γ-Aminobutyric acidA or C receptor? γ- Aminobutyric acid α1 receptor RNA induces bicuculline-, barbiturate-, and benzodiazepine-insensitive γ-aminobutyric acid responses inXenopus oocytes.Mol. Pharmacol. 41, 683–687.PubMedGoogle Scholar
  329. Shingai R., Sutherland M. L. and Barnard E. A. (1991) Effects of subunit types of the cloned GABAA receptor on the response to a neurosteroid.Eur. J. Pharmacol. 206, 77–80.PubMedCrossRefGoogle Scholar
  330. Shivers B. D., Killisch I., Sprengel R., Sontheimer H., Köhler M., Schofield P. R. and Seeburg P. H. (1989) Two novel GABAA receptor subunits exist in distinct neuronal subpopulations.Neuron 3, 327–337.PubMedCrossRefGoogle Scholar
  331. Sieghart W. (1983) Several new benzodiazepines selectively interact with a benzodiazepine receptor subtype.Neurosci. Lett. 38, 73–78.PubMedCrossRefGoogle Scholar
  332. Sieghart W. (1994) Pharmacology of benzodiazepine receptors: an update.J. Psychiatry Neurosci. 19, 24–29.PubMedGoogle Scholar
  333. Sieghart W. (1995) Structure and pharmacology of γ-aminobutyric acidA receptor subtypes.Pharmacol. Rev. 47, 181–234.PubMedGoogle Scholar
  334. Sigel E. and Barnard F. A. (1984) A γ-aminobutyric acid/benzodiazepine receptor complex from bovine cerebral cortex. Improved purification with preservation of regulatory sites and their interactions.J. Biol. Chem. 259, 7219–7223.PubMedGoogle Scholar
  335. Sigel E., Baur R. and Malherbe P. (1993) Recombinant GABAA receptor function and ethanol.FEBS Lett. 324, 140–142.PubMedCrossRefGoogle Scholar
  336. Sigel E., Baur R., Kellenberger S. and Malherbe P. (1992) Point mutations affecting antagonist affinity and agonist dependent gating of GABAA receptor channels.EMBO J. 11, 2017–2023.PubMedGoogle Scholar
  337. Sigel E., Baur R., Malherbe P. and Möhler H. (1989) The rat β1-subunit of the GABAA receptor forms a picrotoxin-sensitive anion channel open in the absence of GABA.FEBS Lett. 257, 377–379.PubMedCrossRefGoogle Scholar
  338. Sigel E., Baur R., Trube G., Möhler H. and Malherbe P. (1990) the effect of subunit composition of rat brain GABAA receptors on channel function.Neuron 5, 703–711.PubMedCrossRefGoogle Scholar
  339. Sigel E., Stephenson F. A., Mamalaki C. and Barnard E. A. (1983) A γ-aminobutyric acid/benzodiazodiazepine receptor complex of bovine cerebral cortex.J. Biol. Chem. 258, 6965–6971.PubMedGoogle Scholar
  340. Sigel, E. and Kannenberg, K. (1996) GABAA receptor subtypes.Trends Neurosci. 19, 386.PubMedCrossRefGoogle Scholar
  341. Sivilotti L. and Nistri A. (1991) GABA receptor mechanisms in the central nervous system.Prog. Neurobiol. 36, 35–92.PubMedCrossRefGoogle Scholar
  342. Sivilotti, L. and Nistri, A. (1989) Pharmacology of a novel effect of γ-aminobutyric acid on the frog optic tectum in vitro.Eur. J. Pharmacol. 164, 205–212.PubMedCrossRefGoogle Scholar
  343. Skerritt J. H. and Johnston G. A. (1983) Interactions of some anaesthetic, convulsant, and anticonvulsant drugs at GABA-benzodiazepine receptorionophore complexes in rat brain synaptosomal membranes.Neurochem. Res. 8, 1351–1362.PubMedCrossRefGoogle Scholar
  344. Skolnick P., Trullas R., Havoundjian H. and Paul S. (1986) The benzodiazepine/GABA receptor complex in anxiety.Clin. Neuropharmacol. 4, 43–45.Google Scholar
  345. Slany A., Zezula J., Fuchs K. and Sieghart W. (1995) Allosteric modulation of [3H]flunitrazepam binding to recombinant GABAA receptors.Eur. J. Pharmacol-Molec. Pharm. 291, 99–105.CrossRefGoogle Scholar
  346. Slany A., Zezula J., Tretter V. and Sieghart W. (1995) Rat β 3 subunits expressed in human embryonic kidney 293 cells form high affinity [35S]t-butylbicyclophosphorothionate binding sites modulated by several allosteric ligands of γ-aminobutyric acid type a receptors.Mol. Pharmacol. 48, 385–391.PubMedGoogle Scholar
  347. Smart T. G. and Constanti A. (1990) Differential effect of zinc on the vertebrate GABAA-receptor complex.Br. J. Pharmacol. 99, 643–654.PubMedGoogle Scholar
  348. Smith G. B. and Olsen R. W. (1994) Identification of a [3H]muscimol photoaffinity substrate in the bovine γ-aminobutyric acidA receptor α subunit.J. Biol. Chem. 269, 20,380–20,387.Google Scholar
  349. Smith G. B. and Olsen R. W. (1995) Functional domains of GABAA receptors.Trends Pharmacol. Sci. 16, 162–168.PubMedCrossRefGoogle Scholar
  350. Squires R. F. and Saederup E. (1987) GABAA receptor blockers reverse the inhibitory effect of GABA on brain-specific [35S]TBPS binding.Brain Res. 414, 357–364.PubMedCrossRefGoogle Scholar
  351. Squires R. F., Benson D. I., Braestrup C., Coupet J., Klepner C. A., Myers V. and Beer B. (1979) Some properties of brain specific benzodiazepine receptors: new evidence for multiple receptors.Pharmacol. Biochem. Behav. 10, 825–830.PubMedCrossRefGoogle Scholar
  352. Squires R. F., Casida J. E., Richardson M. and Saederup E. (1983) [35S]t-butylbicyclophosphorothionate binds with high affinity to brain-specific sites coupled to γ-aminobutyric acidA and ion recognition sites.Mol. Pharmacol. 23, 326–336.PubMedGoogle Scholar
  353. Staley K. J., Soldo B. L. and Proctor, W. R. (1995) Ionic mechanisms of neuronal excitation by inhibitory GABAA receptors.Science 269, 977–981.PubMedCrossRefGoogle Scholar
  354. Staley K., Smith R., Schaack, J., Wilcox, C. and Jentsch, T. J. (1996) Alteration of GABAA receptor function following gene transfer of the CLC-2 chloride channel.Neuron 17, 543–551.PubMedCrossRefGoogle Scholar
  355. Stevenson A., Wingrove P. B., Whiting P. J. and Wafford K. A. (1995) β-Carboline γ-aminobutyric acidA receptor inverse agonists modulate γ-aminobutyric acid via the loreclezole binding site as well as the benzodiazepine site.Mol. Pharmacol. 48, 965–969.PubMedGoogle Scholar
  356. Strata F. and Cherubini, E. (1994) Transient expression of a novel type of GABA response in rat CA3 hippocampal neurones during development.J. Physiol. Lond. 480, 493–503.PubMedGoogle Scholar
  357. Study, R. E. and Barker, J. L. (1981) Diazepam and pentobarbital: fluctuation analysis reveals different mechanisms for potentiation of γ-aminobutyric acid responses in cultured central neurons.Proc. Natl. Acad. Sci. USA 78, 7180–7184.PubMedCrossRefGoogle Scholar
  358. Supavilai P. and Karobath M. (1983) Differential modulation of [35S]TBPS binding by the occupancy of benzodiazepine receptors with its ligands.Eur. J. Pharmacol. 91, 145–146.PubMedCrossRefGoogle Scholar
  359. Suzdak P. D., Glowa J. R., Crawley J. N., Schwartz R., Skolnick P. and Paul S. M. (1986) A Selective Imidazobenzodiazepine Antagonist of Ethanol in the Rat.Science 234, 1243–1247.PubMedCrossRefGoogle Scholar
  360. Suzdak P. D., Paul S. M. and Crawley J. N. (1988) Effects of Ro15-4513 and other benzodiazepine receptor inverse agonists on alcohol-induced intoxication in the rat.J. Pharmacol. Exp. Ther. 245, 880–886.PubMedGoogle Scholar
  361. Tabakoff B. and Hoffman P. L. (1996) Alcohol addiction: an enigma among us.Neuron 16, 909–912.PubMedCrossRefGoogle Scholar
  362. Taguchi J. and Kuriyama K. (1990) Functional modulation of cerebral γ-aminobutyric acidA receptor/benzodiazepine receptor/chloride ion channel complex with ethyl β-carboline-3-carboxylate: presence of independent binding site for ethyl β-carboline-3-carboxylate.J. Pharmacol. Exp. Ther. 253, 558–566.PubMedGoogle Scholar
  363. Taleb O., Trouslard J., Demeneix B. A., Feltz P., Bossu J. L., Dupont J. L. and Feltz A. (1987) Spontaneous and GABA-evoked chloride channels on pituitary intermediate lobe cells and their internal Ca requirements.Pflugers. Arch. 409, 620–631.PubMedCrossRefGoogle Scholar
  364. Tallman J. F., Thomas J. W. and Gallager, D. W. (1978) GABAergic modulation of benzodiazepine binding site sensitivity.Nature 288, 609–610.Google Scholar
  365. Thomas, J. W. and Tallman, J. F. (1983) Photoaffinity labeling of benzodiazepine receptors causes altered agonist- antagonist interactions.J. Neurosci. 3, 433–440.PubMedGoogle Scholar
  366. Thompson S. M. and Gahwiler B. H. (1989) Activity-dependent disinhibition. II. Effects of extracellular potassium, furosemide, and membrane potential on ECI-in hippocampal CA3 neurons.J. Neurophysiol. 61, 512–523.PubMedGoogle Scholar
  367. Thompson S. M., Deisz R. A. and Prince D. A. (1988) Relative contributions of passive equilibrium and active transport to the distribution of chloride in mammalian cortical neurons.J. Neurophysiol. 60, 105–124.PubMedGoogle Scholar
  368. Ticku M. K. and Olsen R. W. (1978) Interaction of barbiturates with dihydropicrotoxinin binding sites related to the GABA receptor-ionophore system.Life Sci. 22, 1643–1651.PubMedCrossRefGoogle Scholar
  369. Tierney M. L., Birnir B., Pillai N. P., Clements J. D., Howitt S. M., Cox G. B. and Gage P. W. (1996) Effects of mutating leucine to threonine in the M2 segment of α1 and β1 subunits of GABAA α1 β1 receptors.J. Mem. Biol. 154, 11–21.CrossRefGoogle Scholar
  370. Tretter, V., Ehya, N., Fuchs, K. and Sieghart, W. (1997) Stoichiometry and assembly of a recombinant GABAA receptor subtype.J. Neurosci. 17, 2728–2737.PubMedGoogle Scholar
  371. Trifiletti, R. R. and Snyder, S. H. (1984) Anxiolytic cyclopyrrolones zopiclone and suriclone bind to a novel site linked allosterically to benzodiazepine receptors.Mol. Pharmacol. 26, 458–469.PubMedGoogle Scholar
  372. Trifiletti, R. R., Snowman, A. M. and Snyder, S. H. (1984) Anxiolytic cyclopyrrolone drugs allosterically modulate the binding of [35S]t-butylbicyclophosphorothionate to the benzodiazepine/γ-aminobutyric acid-A receptor/chloride anionophore complex.Mol. Pharmacol. 26, 470–476.PubMedGoogle Scholar
  373. Tsoi W. F. (1991) Insomnia: drug treatment.Ann. Acad. Med. Singapore 20, 269–272.PubMedGoogle Scholar
  374. Turner, D. M., Ransom, R. W., Yang, J. S. and Olsen, R. W. (1989) Steroid anesthetics and naturally occurring analogs modulate the γ-aminobutyric acid receptor complex at a site distinct from barbiturates.J. Pharmacol. Exp. Ther. 248, 960–966.PubMedGoogle Scholar
  375. Twyman R. E. and Macdonald R. L. (1992) Neurosteroid regulation of GABAA receptor single-channel kinetic properties of mouse spinal cord neurons in culture.J. Physiol. Lond. 456, 215–245.PubMedGoogle Scholar
  376. Twyman R. E., Rogers C. J. and Macdonald R. L. (1989a) Pentobarbital and picrotoxin have recip-rocal actions on single GABAA receptor channels.Neurosci. Lett. 96, 89–95.PubMedCrossRefGoogle Scholar
  377. Twyman R. E., Rogers C. J. and Macdonald R. L. (1989b) Differential regulation of γ-aminobutyric acid receptor channels by diazepam and phenobarbital.Ann. Neurol. 25, 213–220.PubMedCrossRefGoogle Scholar
  378. Twyman R. E., Rogers C. J. and Macdonald R. L. (1990) Intraburst kinetic properties of the GABAA receptor main conductance state of mouse spinal cord neurones in culture.J. Physiol. Lond. 423, 193–220.PubMedGoogle Scholar
  379. Twyman R. E., Green R. M. and Macdonald, R. L. (1992) Kinetics of open channel block by penicillin of single GABAA receptor channels from mouse spinal cord neurones in culture.J. Physiol. Lond. 445, 97–127.PubMedGoogle Scholar
  380. Unwin N. (1989) The structure of ion channels in membranes of excitable cells.Neuron 3, 665–676.PubMedCrossRefGoogle Scholar
  381. Unwin N. (1993) Nicotinic acetylcholine receptor at 9 A resolution.J. Mol. Biol. 229, 1101–1124.PubMedCrossRefGoogle Scholar
  382. Unwin N. (1995) Acetylcholine receptor channel imaged in the open state.Nature 373, 37–43.PubMedCrossRefGoogle Scholar
  383. Uusi Oukari M. and Korpi E. R. (1989) Cerebellar GABAA receptor binding and function in vitro in two rat lines developed for high and low alcohol sensitivity.Neurochem. Res. 14, 733–739.PubMedCrossRefGoogle Scholar
  384. Van Renterghem C., Bilbe G., Moss S., Smart T. G., Constanti A., Brown D. A. and Barnard E. A. (1987) GABA receptors induced in Xenopus oocytes by chick brain mRNA: evaluation of TBPS as a use-dependent channel-blocker.Brain Res. 388, 21–31.PubMedGoogle Scholar
  385. Varecka, L., Wu C. H., Rotter A. and Frostholm, A. (1994) GABAA/benzodiazepine receptor α6 subunit mRNA granule cells of the cerebellar cortex and cochlear nuclei: expression in developing and mutant mice.J. Comp. Neurol. 339, 341–352.PubMedCrossRefGoogle Scholar
  386. Verdoorn T. A. (1994) Formation of heteromeric γ-aminobutyric acid type A receptors containing two different α subunits.Mol. Pharmacol. 45, 475–480.PubMedGoogle Scholar
  387. Verdoorn T. A., Draguhn A., Ymer S., Seeburg P. H. and Sakmann B. (1990) Functional properties of recombinant rat GABAA receptors depend upon subunit composition.Neuron 4, 919–928.PubMedCrossRefGoogle Scholar
  388. von Blankenfeld G., Ymer S., Pritchett D. B., Sontheimer H., Ewert M., Seeburg P. H. and Kettenmann H. (1990) Differential benzodiazepine pharmacology of mammalian recombinant GABAA receptors.Neurosci. Lett. 115, 269–273.CrossRefGoogle Scholar
  389. von Blankenfeld, G. and Kettenmann H. (1991) Glutamate and GABA receptors in vertebrate glial cells.Mol. Neurobiol. 5, 31–43.Google Scholar
  390. Wafford K. A. and Whiting P. J. (1992) Ethanol potentiation of GABAA receptors requires phosphorylation of the alternatively spliced variant of the γ2 subunit.FEBS Lett. 313, 113–117.PubMedCrossRefGoogle Scholar
  391. Wafford K. A., Bain C. J., Quirk K., Mckernan R. M., Wingrove P. B., Whiting P. J. and Kemp J. A. (1994) A novel allosteric modulatory site on the GABAA receptor β subunit.Neuron 12, 775–782.PubMedCrossRefGoogle Scholar
  392. Wafford, K. A., Whiting, P. J. and Kemp, J. A. (1993a) Differences in affinity and efficacy of benzodiazepine receptor ligands at recombinant γ-aminobutyric acidA receptor subtypes.Mol. Pharmacol. 43, 240–244.PubMedGoogle Scholar
  393. Wafford K. A., Bain C. J., Whiting P. J. and Kemp J. A. (1993b) Functional comparison of the role of γ subunits in recombinant human γ-aminobutyric acidA/benzodiazepine receptors.Mol. Pharmacol. 44, 437–442.PubMedGoogle Scholar
  394. Wafford, K. A., Burnett, D. M., Leidenheimer, N. J., Burt, D. R., Wang, J. B., et al. (1991) Ethanol sensitivity of the GABAA receptor expressed inXenopus oocytes requires 8 amino acids contained in the γ2L subunit.Neuron 7, 27–33.PubMedCrossRefGoogle Scholar
  395. Wakamori M., Ikemoto Y. and Akaike N. (1991) Effects of two volatile anesthetics and a volatile convulsant on the excitatory and inhibitory amino acid responses in dissociated CNS neurons of the rat.J. Neurophysiol. 66, 2014–2021.PubMedGoogle Scholar
  396. Weissman B. A., Cott J., Hommer D., Quirion R., Paul S. and Skolnick P. (1983) Pharmacological, electrophysiological, and neurochemical actions of the convulsant benzodiazepine Ro 5-4864 (4′-chlordiazepam).Adv. Biochem. Psychopharmacol. 38, 139–151.PubMedGoogle Scholar
  397. White G. and Gurley D. A. (1995) α subunits influence Zn block of γ 2 containing GABAA receptor currents.Neuroreport 6, 461–464.PubMedCrossRefGoogle Scholar
  398. White, G. (1992) Heterogeneity in EC50 and nM of GABAA receptors on dorsal root ganglion neurons freshly isolated from adult rats.Brain Res. 585, 56–62.PubMedCrossRefGoogle Scholar
  399. Whiting P., McKernan R. M. and Iversen, L. L. (1990) Another mechanism for creating diversity in γ-aminobutyrate type A receptors: RNA splicing directs expression of two forms of γ2 phosphorylation site.Proc. Natl. Acad. Sci. USA 87, 9966–9970.PubMedCrossRefGoogle Scholar
  400. Wieland H. A. and Lüddens H. (1994) Four amino acid exchanges convert a diazepam-insensitive, inverse agonist-preferring GABAA receptor into a diazepam-preferring GABAA receptor.J. Med. Chem. 37, 4576–4580.PubMedCrossRefGoogle Scholar
  401. Wieland H., Lüddens H. and Seeburg P. H. (1992) A single histidine in GABAA receptors is essential for benzodiazepine agonist binding.J. Biol. Chem. 257, 1426–1429.Google Scholar
  402. Wilke K., Gaul R. and Poustka A. (1997) Complex alternative splicing as a mechanism for tissue specific expression of a gene defining the putative new subunit class ε of the GABAA neurotransmitter receptor (submitted).Google Scholar
  403. Williamson, R. E. and Pritchett, D. B. (1994) Levels of benzodiazepine receptor subtypes and GABAA receptor α-subunit mRNA do not correlate during development.J. Neurochem. 63, 413–418.PubMedCrossRefGoogle Scholar
  404. Wingrove P. B., Wafford K. A., Bain C. and Whiting P. J. (1994) The modulatory action of loreclezole at the γ-aminobutyric acid type A receptor is determined by a single amino acid in the β2 and β3 subunit.Proc. Natl. Acad. Sci. USA 91, 4569–4573.PubMedCrossRefGoogle Scholar
  405. Wisden W., Herb A., Wieland H., Keinanen K., Lüddens H. and Seeburg P. H. (1991) Cloning, pharmacological characteristics and expression pattern of the rat GABAA receptor α 4 subunit.FEBS Lett. 289, 227–230.PubMedCrossRefGoogle Scholar
  406. Wisden W., Laurie D. J., Monyer H. and Seeburg P. H. (1992) The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, Diencephalon, Mesencephalon.J. Neurosci. 12, 1040–1062.PubMedGoogle Scholar
  407. Wisden W., Gundlach A. L., Barnard E. A., Seeburg, P. H. and Hunt S. P. (1991) Distribution of GABAA receptor subunit mRNAs in rat lumbar spinal cord.Brain Res. Mol. Brain Res. 10, 179–183.PubMedCrossRefGoogle Scholar
  408. Wong D. T., Threlkeld P. G., Bymaster F. P. and Squires R. F. (1984) Saturable binding of35S-t-butylbicyclophosphorothionate to the sites linked to the GABA receptor and the interaction with GABAergic agents.Life Sci. 34, 853–860.PubMedCrossRefGoogle Scholar
  409. Wong G. and Skolnick P. (1992) High affinity ligands for ‘diazepam-insensitive’ benzodiazepine receptors.Eur. J. Pharmacol. 225, 63–68.PubMedCrossRefGoogle Scholar
  410. Wong G., Sei Y. and Skolnick P. (1992) Stable expression of type I γ-aminobutyric acidA/benzodiazepine receptors in a transfected cell line.Mol. Pharmacol. 42, 996–1003.PubMedGoogle Scholar
  411. Xu M. and Akabas M. H. (1996) Identification of channel-lining residues in the M2 membrane-spanning segment of the GABAA receptor α1 subunit.J. Gen. Physiol. 107, 195–205.PubMedCrossRefGoogle Scholar
  412. Xu M., Covey D. F. and Akabas M. H. (1995) Interaction of picrotoxin with GABAA receptor channel-lining residues probed in cysteine mutants.Biophys. J. 69, 1858–1867.PubMedGoogle Scholar
  413. Yakushiji T., Fukuda T., Oyama Y. and Akaike N. (1989) Effects of benzodiazepines and non-benzodiazepine compounds on the GABA-induced response in frog isolated sensory neurones.Br. J. Pharmacol. 98, 735–740.PubMedGoogle Scholar
  414. Yakushiji T., Tokutomi N. and Akaike N. (1989) Augmentation of GABA-induced chloride current in frog sensory neurons by diazepam.Neurosci. Res. 6, 309–320.PubMedCrossRefGoogle Scholar
  415. Yang J., Isenberg K. E. and Zorumski C. F. (1992) Volatile anesthetics gate a chloride current in postnatal rat hippocampal neurons.FASEB J. 6, 914–918.PubMedGoogle Scholar
  416. Yang J. S. and Olsen R. W. (1987) γ-Aminobutyric acid receptor-regulated36Cl-flux in mouse cortical slices.J. Pharmacol. Exp. Ther. 241, 677–685.PubMedGoogle Scholar
  417. Ymer S., Draguhn A., Wisden W., Werner P., Keinänen K. et al. (1990) Structural and functional characterization of the γ1 subunit of GABAA/benzodiazepine receptors.EMBO J. 9, 3261–3267.PubMedGoogle Scholar
  418. Ymer S., Schofield P. R., Draguhn A., Werner P., Köhler M. and Seeburg P. H. (1989) GABAA receptor β subunit heterogeneity: functional expression of cloned cDNAs.EMBO J. 8, 1665–1670.PubMedGoogle Scholar
  419. Yoon K. W., Covey D. F. and Rothman S. M. (1993) Multiple mechanisms of picrotoxin block of GABA-induced currents in rat hippocampal neurons.J. Physiol. Lond. 464, 423–439.PubMedGoogle Scholar
  420. Zaman S. H., Shingai R., Harvey R. J., Darlison M. G. and Barnard E. A. (1992) Effects of subunit types of the recombinant GABAA receptor on the response to a neurosteroid.Eur. J. Pharmacol. 225, 321–330.PubMedCrossRefGoogle Scholar
  421. Zdilar D., Luntz Leybman V., Frostholm A. and Rotter A. (1992) Differential expression of GABAA/benzodiazepine receptor β1, β2, and β3 subunit mRNAs in the developing mouse cerebellum.J. Comp. Neurol. 326, 580–594.PubMedCrossRefGoogle Scholar
  422. Zezula J., Slany A. and Sieghart W. (1996) Interaction of allosteric ligands with GABAA receptors containing one, two, or three different subunits.Eur. J. Pharmacol. 301, 207–214.PubMedCrossRefGoogle Scholar
  423. Zhang L., Spigelman I. and Carlen P. L. (1991) Development of GABA-mediated, chloride-dependent inhibition in CA1 pyramidal neurones of immature rat hippocampal slices.J. Physiol. Lond. 444, 25–49.PubMedGoogle Scholar
  424. Zhang, J. H., Sato, M. and Tohyama, M. (1991) Region-specific expression of the mRNAs encoding β subunits (β1, β2, and β3) of GABAA receptor in the rat brain.J. Comp. Neurol. 303, 637–657.PubMedCrossRefGoogle Scholar
  425. Zhu W. J., Wang J. F., Krueger K. E. and Vicini S. (1996) δ subunit inhibits neurosteroid modulation of GABAA receptors.J. Neurosci. 16, 6648–6656.PubMedGoogle Scholar

Copyright information

© Humana Press Inc 1998

Authors and Affiliations

  • Wulf Hevers
    • 1
  • Hartmut Lüddens
    • 1
  1. 1.Wulf Hevers & Hartmut Lüddens Clinical Research Group, Department of PsychiatryUniversity of MainzMainzGermany

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