Abstract
Glutamate stimulated release of [3H]GABA was studied, during receptor desensitization block and its modulation by voltage gated Ca2+ channels, internal Ca2+ mobilization and GABA transport inhibitors from olfactory bulb slices. Under control conditions, glutamate and agonists induced release was strongly inhibited by Mg/0 Ca2+ Krebs and Cd2+ and partially inhibited by Ni2+ and nifedipine. Cyclothiazide, which blocks desensitization of glutamate receptors, potentiated glutamate, kainate, AMPA and quisqualate induced release. This effect was less dependent of entry of external Ca2+, but was inhibited by trifluoperazine and thapsigargin, inhibitors of Ca2+-calmodulin and endoplasmatic Ca2+ ATPase respectively. Nipecotic acid and NO-711, inhibitors of the GABA transporter, were also able to reduce cyclothiazide potentiated release induced by the 4 secretagogues. Under control conditions, glutamate stimulates the release of GABA in cooperation with VDCC. However, during receptor desensitization block, glutamate stimulated GABA release is mainly modulated through mechanisms dependent on internal Ca2+ mobilization and reversal of the GABA transporter.
Similar content being viewed by others
REFERENCES
Attwell, D., Barbour, B., and Szatkowski, M. 1993. Nonvesicular release of neurotransmitter. Neuron 11:401–407.
Levi, G. and Raiteri, M. 1993. Carrier-mediated release of neurotransmitters. TINS 16:415–419.
Dunlap, K., Luebke, J. I., and Turner, T. J. 1995. Exocytotic Ca2+ channels in mammalian central neurons. Trends Neurosci. 18:89–98.
Zhang, J.-F., Rndall, A. D., Ellinor, T., Horne, W. A., Sather, W. A., Tanabe, T., Schwarz, T. L., and Tsien, R. W. 1993. Distinctive pharmacology and kinetics of cloned neuronal Ca2+ channels and their possible counterparts in mammalian CNS neurons. Neuropharmacol. 32:1075–1088.
Dingledine, R., Borges, K., Bowie, D., and Traynelis, S. F. 1999. The Glutamate receptor ion channels. Pharmacology Reviews 51:7–61. 4.
Acher, P. and Nowak, L. 1987. Electrophysiological studies of NMDA receptors. TINS 10:284–288.
Hollmann, M., Hartley, M., and Heinemann, S. 1991. Ca2+ permeability of KA-AMPA-Gated glutamate receptor channels depends on subunit composition. Science 252:1028–1031.
Verdoorn, T. A., Burnashev, N., Monyer, H., Seeburg, P. H., and Sakmann, B. 1991. Structural determinants of ion flow through recombinant glutamate receptor channels. Science 522:1715–1718.
Simpson, P. B., Challiss, R. A., and John Nahorski, S. R. 1995. Neuronal Ca2+ stores: activation and function. Trends Neurosci. 18:299–306.
Berridge, M. J. 1998. Neuronal calcium signaling. Neuron 21:13–26.
Fossier, P., Tauc, L., and Baux. G. 1999. Calcium transients and neurotransmitter release at an identified synapse. Trends Neurosci. 22:161–166.
Kenigsberg, R. L. and Trifaró, J. M. 1985. Microinjection of calmodulin antibodies into cultured chromaffin cells blocks catecholamine release in response to stimulation. Neuroscience 14:335–347.
Burgoyne, R. D. and Morgan, A. 1995. Ca2+ and secretoryvesicle dynamics. Trends Neurosci. 18:191–196.
Ghosh, A. and Greenberg M. E. 1995. Calcium signalling in neurons: molecular mechanisms and cellular consecuences. Science 268:239–247.
David J. C., Yamada K. A., Bagwe M. R., and Goldberg, M. P. 1996. AMPA receptor activation is rapidly toxic to cortical astrocytes when desensitization is blocked. J. Neurosci. 16:200–209.
Ambrosio, A. F., Silva, A. P., Malva, J. O., Mesquita, J. F., Carvalho, A. P., and Carvalho, C. M. 2000. Role of desensitization of AMPA receptors on the neuronal viability and on the [Ca++]i changes in cultured rat hippocampal neurons. Eur. J. Neurosci. 12:2021–2031.
Fradsen, A. and Schousboe, A. 1993. Excitatory amin acid mediated cytotoxicity and calcium homeostasis in cultural neurons J. Neurochem. 60:1202–1211.
Shepherd, G. and Greer, C. 1990. Olfactory bulb, in Synaptic Organization of the Brain (Shepherd G. M., ed), Oxford University Press, Oxford. 133–169.
Jaffé, E. H. and Vaello, M. L. 1989. Release of γ-[3H]Aminobutyric acid from rat olfactory bulb and substantia nigra: differential modulation by glutamic acid. J. Neurochem. 52:1766–1774.
Montague, A. A. and Greer, C. A. 1999. Differential distribution of ionotropic glutamate receptor subunits in the rat olfactory bulb. J. Comp. Neurol. 405:233–246.
Monaghan, D. T. and Cotman, C. W. 1985. Distribution of N-methyl-D-aspartate-sensitive L-3H-glutamate-binding sites in rat brain. J. Neurosci. 5:2909–2919.
Petralia, R. S. and Wenthold, R. J. 1992. Light and electron immunocytochemical localization of AMPA-selective glutamate receptors in rat brain. J. Comp. Neurol. 318:329–354.
Unnerstall, J. and Wamsley, J. 1983. Autoradiographic localization of high-affinity 3H-kainic acid binding sites in the rat forebrain. Eur. J. Pharmacol. 86:361–371.
Trombley, P. Q. and Shepherd, G. M. 1993. Synaptic transmission and modulation in the olfactory bulb. Curr. Opin. Neurobiol. 3:540–547.
Pognetto-Sassoe, M. and Ottersen, O. P. 2000. Organization of ionotropic glutamate receptors at dendrodendritic synapses in the rat olfactory bulb. J. Neuroscience 20:2192–2201.
Isaacson, J. S. and Strowbridge, B. W. 1998. Olfactory reciprocal synapses: dendritic signaling in the CNS. Neuron 20:749–761.
Jahr, C. E. and Nicoll, P. A. 1982. An intracellular analysis of dendrodendritic inhibition in the turtle in vitro olfactory bulb. J. Physiol. (Lond.) 326:213–234.
Jacobson, I., Butcher, S., and Hamberger, A. 1986. An analysis of the effects of excitatory amino acid receptor antagonists on evoked filed potentials in the olfactory bulb. Neuroscience 19:267–273.
Halabisky, B., Friedman, D., Radojicic, M., and Srtowbridge, B. W. 2000. Calcium influx through NMDA receptors directly evokes GABA release in olfactory bulb granule cells. J. Neuroscience 20:5124–5134.
Jaffé, E. H. and Garcia, Y. 1997. Excitatory sulfur-containing amino acid-induced release of [3H]GABA from rat olfactory bulb. Neurochem Res. 22:1477–1484.
Jaffé, E. H. and Cuello, A. C. 1980. Release of g-aminobutyrate from the external plexiform layer of the rat olfactory bulb: possible dendritic involvement. Neuroscience 5:1859–1869.
Sokal, R. R. and Rohlf, F. J. 1969. Biometry. W. H. Freeman and Co., San Francisco, California.
Fox, A. P., Nowycky, M. C., and Tsien, R. W. 1987. Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones. J. Physiol. 394:149–172.14.
Yamada, K. A. and Rothman, S. M. 1992. Diazoxide blocks glutamate desensitization and prolongs excitatory postsynaptic currents in rat hippocampal neurons. J. Physiol. (Lond.) 458:409–423.
Partin, K. M., Patneau, D. K., Winters, C. A., Mayer, M. L., and Buonanno, A. 1993. Selective modulation of desensitization at AMPA versus kainate receptors by cyclothiazide and concanavalin A. Neuron 11:1069–1082.
Desai, M. A., Burnett, J. P., and Schoepp, D. D. 1994. Cyclothiazide selectively potentiates AMPA-and kainate-induced [3H]norepinephrine release from rat hippocampal slices. J. Neurochem. 63:231–237.
Hoyt, K. R., Rajdev, S., Fattman, Ch. L., and Reynolds, I. J. 1995. Cyclothiazide modulates AMPA receptor-mediated increases in intracellular free Ca2+ and Mg2+ in cultured neurons from rat brain. J. Neurochem. 64:2049–2056.
Zorumski, C. V., Yamada, K. A., Price, M. T., and Olney, J. W. 1993. A benzodiazepine recognition site associated with the non-NMDA glutamate receptor. Neuron 10:61–67.
Mosbacher, J., Schoepfer, R., Monyer, H., Burnashev, N., Seeburg, P. H., and Ruppersberg J. P. 1994. A molecular determinant for submillisecond desensitization in glutamate receptors. Science 266:1059–1062.
Vorobjev, V. S., Sharonova, I. N., Haas H. L., and Sergeeva, O. A. 2000. Differential modulation of AMPA receptors by cyclothiazide in two types of striatal neurons. Eur. J. Neurosci. 12:2871–2880.
Roufogalis, B. D., Minocherhomjee, A. M., and Al-Jobore, A. 1983. Pharmacological antagonism of calmodulin. Can. J. Biochem. Cell. Biol. 61:927–933.
Thastrup, O., Cullen, P. J., Drobak, B. K., Hanley, M. R., and Dawson, A. P. 1990. Thapsigargin, a tumor promoter, discharges intacellular Ca2+ stores by specific inhibition of the endoplasmatic reticulum Ca2+-ATPase. Proc. Natl. Acad. Sci. 8:2466–2470.
Demaurex, N., Lew, D. P., and Krause K. H. 1992. Cyclopiazonic acid depletes intracellular Ca++ stores and activates an influx pathway for divalent cations in HL-60 cells. J. Biol. Chem. 267:2318–2324.
Krogsgaard-Larsen, P. and Johnston, G. A. 1975. Inhibition of GABA uptake in rat brain slices by nipecotic acid, various isoxasoles and related compounds. J. Neurochem. 25:797–802.
Kanner, B. I. and Bendahan Radian, R. 1983. Efflux and exchange of g-aminobutyric acid and nipecotic acid catalysed by synaptic plasma membrane vesicle isolated fromimmature rat brain, Biochem. Biophys. Acta 731:54–62.
Dong, C.-J., Picaud, S. A., and Werblin, F. S. 1994. GABA transporters and GABAc-like receptors on catfish cone but not rod hotizontal cells. J. Neuroscience 14:2649–2658.
Watkins, J. C., Krogsgaard-Larsen, P., and Honore, T. 1990. Structure-activity relationship in the development of excitatory amino acid receptor agonists and competitive antagonist. TIPS 11:25–33.
García, Y., Ibarra, C., and Jaffé, E. H. 1995. NMDA and Non-NMDA Receptor-Mediated Release of [3H]GABA from granule cell dendrites of rat olfactory bulb. J. Neurochem. 64:662–669.
Bishofberger, J. and Schild, D. 1995. Different spatial patterns of [Ca2+] increase caused by N-and L-type Ca2+ channel activation in frog olfactory bulb neurones. J. Physiol. 487:305–317.
Zhou, Z. and Neher, E. 1993. Mobile and immobile calcium buffers in bovine adrenal chromaffin cells. J. Physiol. 469:245–273.
Greengard, P., Valtorat, F., Czernik, A. J., and Benfenati, F. 1993. Synaptic vesicle phosphoproteins and regulation of synaptic function. Science 259:780–785.
Risinger, C. and Bennett, M. K. 1999. Differential phosphorylation of syntaxin and synaptosome-associated protein of 25 kDA (SNAP-25) isoforms. J. Neurochem. 72:614–624.
Hashimoto, T., Ishii, T., and Ohmori, H. 1996. Release of Ca2+ is the crucial step for the potentiation of IPSCs in the culturaed cerebellar Purkinje cells of the rat. J. Physiol. 497:611–627.
Wulfert, E. and Margineanu, D. G. 1998. Thapsigargin inhibits bicuculline-induced epileptiform excitability in rat hippocampal slices. Neurosci. Lett. 243:141–143.
Akopian, A., Gabriel, R., and Witkovsky, P. 1998. Calcium release from intracellular stores inhibits GABAA-mediated currents in ganglion cells of the turtle retina. J. Neurophysiol. 80:1105–1115.
Savik, N. and Sciancalepore, M. 1998. Intracllular calcium stores modulate miniature GABA-mediated synaptic currents in neonatal rat hippocampal neurons. Eur. J. Neurosci. 10:3379–3386.
Itoh, T., Itoh, A., Horiuchi, K., and Pleasure, D. 1998. AMPA receptor-mediated excitotoxicity in human NT2-N neurons results from loss of intracellular Ca2+ homeostasis following marked elevation of intracellular Na+. J. Neurochem. 71:112–124.
Cowen, M. S. and Beart, P. M. 1998. Cyclothiazide and AMPA receptor desensitization: analyses from studies of AMPA-induced release of [3H]-noradrenaline from hippocampal slices. Br. J. Pharmacol. 123:473–480.
Jaffé, E. H., Rodriquez, A., and Figueroa, L. 1998. Ca2+ dependency of glutamate stimulated [3H]-GABA release from granule cell dendrites of rat olfactory bulb. Society Neuroscin. Abstracts 2:1314.
Alford, S., Frenguelli, B. G., Schofield, J. G., and Collingridge, G. L. 1993. Characterization of Ca2+ signals induced in hippocampal CA1 neurones by the synaptic activation of NMDA receptors. J. Physiol. 469:693–716.
Müller, W. and Connor, J. A. 1991. Dendritic spines as individual neuronal compartments for synaptic Ca2+ responses. Nature 354:73–76.
Yasuda, H., Kinoshita, S., and Tsumoto, T. 1998. Localized contribution of N-methyl-D-aspartate receptors to synaptic input-induced rise of calcium in apical dendrites of layer II /III neurons in rat visual cortex. Neuroscience 85:1011–1024.
Impagnatiello, F., Oberto, A., Longone, P., Costa, E., and Guidotti, A. 1997. 7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide: a partial modulator of AMPA receptor desensitization devoid of neurotoxicity. Proc. Natl. Acad. Sci. USA 94:7053–7058.
Cebers, G. and Liljequist, S. 1995. Modulation of AMPA/ kainate receptors by cyclothiazide increases cytoplasmic free Ca2+ and 45Ca2+ uptake in brain neurons. Eur. J. Pharmacol. 18:105–115.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jaffe, E.H., Figueroa, L. Glutamate Receptor Desensitization Block Potentiates the Stimulated GABA Release Through External Ca2+-Independent Mechanisms from Granule Cells of Olfactory Bulb. Neurochem Res 26, 1177–1185 (2001). https://doi.org/10.1023/A:1013930803677
Issue Date:
DOI: https://doi.org/10.1023/A:1013930803677