The Cerebellum

, 2:11

What are the roles of the many different types of potassium channel expressed in cerebellar granule cells?

  • Alistair Mathie
  • Catherine E. Clarke
  • Kishani M. Ranatunga
  • Emma L. Veale
Article

Abstract

Potassium (K) channels have a key role in the regulation of neuronal excitability. Over a hundred different subunits encoding distinct K channel subtypes have been identified so far. A major challenge is to relate these many different channel subunits to the functional K currents observed in native neurons. In this review, we have concentrated on cerebellar granule neurons (CGNs). We have considered each of the three principal super families of K channels in turn, namely, the six transmembrane domain, voltage-gated super family, the two transmembrane domain, inward-rectifier super family and the four transmembrane domain, leak channel super family. For each super family, we have identified the subunits that are expressed in CGNs and related the properties of these expressed channel subunits to the functional currents seen in electrophysiological recordings from these neurons. In some cases, there are strong molecular candidates for proteins underlying observed currents. In other cases the correlation is less clear. We show that at least 26 potassium channel a subunits are moderately or strongly expressed in CGNs. Nevertheless, a good empirical model of CGN function has been obtained with just six distinct K conductances. The transient K current in CGNs, seems due to expression of Kv4.2 channels or Kv4.2/4.3 heteromers, while the Kca current is due to expression of large-conductance slo channels. The G-protein activated KIR current is probably due to heteromeric expression of KiR3.1 and KiR3.2. Perhaps KiR2.2 subunits underlie the KiR current when it is constitutively active. The leak conductance can be attributed to TASK-1 and or TASK-3 channels. With less certainty, the IK-slow current may be due to expression of one or more members of the KCNQ or EAG family. Lastly, the delayed-rectifier Kv current has as many as six different potential contributors from the extensive Kv family of α subunits. Since many of these subunits are highly regulated by neurotransmitters, physiological regulators and, often, auxiliary subunits, the resulting electrical properties of CGNs may be highly dynamic and subject to constant fine-tuning.

Keywords

Potassium channels cerebellar granule cells/neurons Kv Kir two pore domain K channels weaver mice 

References

  1. 1.
    Hille B. Ion channels of excitable membranes. Sunderland, MA: Sinauer, 2001.Google Scholar
  2. 2.
    Coetzee WA, Amarillo Y, Chiu J, Chow A, Lau D, McCormack T, Moreno H, Nadal MS, Ozaita A, Pountney D, Saganich M, Vega-Saenz de Miera E, Rudy B. Molecular diversity of K+ channels. Ann NY Acad Sci 1999; 868: 233–285.PubMedCrossRefGoogle Scholar
  3. 3.
    Pongs O. Molecular biology of voltage-dependent potassium channels. Physiol Rev 1992; 72: S69-S88.PubMedGoogle Scholar
  4. 4.
    Chandy KG, Gutman GA. Voltage-gated potassium channel genes. In: North RA, editor. Handbook of receptors and channels: ligand and voltage-gated ion channels. Boca Raton: CRC Press, 1995: 1–71.Google Scholar
  5. 5.
    Dolly O, Parcej DN. Molecular properties of voltage-gated K+ channels. J Bioenerg Biomembr 1996; 28: 231–253.PubMedCrossRefGoogle Scholar
  6. 6.
    Jan LY, Jan YN. Voltage-gated and inwardly rectifying potassium channels. J Physiol 1997; 505: 267–282.PubMedCrossRefGoogle Scholar
  7. 7.
    Nichols CG, Lopatin AN. Inwardly rectifying potassium channels. Ann Rev Physiol 1997; 59: 171–191.CrossRefGoogle Scholar
  8. 8.
    Sanguinetti MC, Spector PS. Potassium channelopathies. Neuropharmacol 1997; 36: 755–762.CrossRefGoogle Scholar
  9. 9.
    Aguilar-Bryan L, Clement JP, Gonzalez G, Kunjilwar K, Babenko A, Bryan J. Toward understanding the assembly and structure of KATP channels. Physiol Rev 1998; 78: 227–245.PubMedGoogle Scholar
  10. 10.
    Mathie A, Wooltorton JRA, Watkins CS. Voltage-activated potassium channels in mammalian neurons and their block by novel pharmacological agents. Gen Pharmacol 1998; 30: 13–24.PubMedGoogle Scholar
  11. 11.
    Bezanilla F. The voltage sensor in voltage-dependent ion channels. Physiol Rev 2000; 80: 555–592.PubMedGoogle Scholar
  12. 12.
    Bauer CK, Schwarz JR. Physiology of EAG channels. J Membrane Biol 2001; 182: 1–15.Google Scholar
  13. 13.
    Robbins J. KCNQ potassium channels: physiology, pathophysiology and pharmacology. Pharmacol Therapeut 2001; 90: 1–19.CrossRefGoogle Scholar
  14. 14.
    Goldstein SAN, Bockenhauer D, O’Kelly I, Zilberberg N. Potassium leak channels and the KCNK family of two-P-domain subunits. Nature RevNeurosci 2001; 2: 175–184.CrossRefGoogle Scholar
  15. 15.
    Herrup K, Kuemerle B. The compartmentalization of the cerebellum. Ann Rev Neurosci 1997; 20: 61–90.PubMedCrossRefGoogle Scholar
  16. 16.
    Voogd J, Glickstein M. The anatomy of the cerebellum. Trends in Neurosci 1998; 21: 370–375.CrossRefGoogle Scholar
  17. 17.
    Rakic P, Sidman RL. Sequence of developmental abnormalities leading to granule cell deficit in cerebellar cortex of weaver mutant mice. J Comp Neuro1 1973; 152: 103–132.CrossRefGoogle Scholar
  18. 18.
    Patil N, Cox DR, Bhat D, Faham M, Myers RM, Peterson AS. A potassium channel mutation in weaver mice implicates membrane excitability in granule cell differentiation. Nature Genetics 1995; 11: 126–129.PubMedCrossRefGoogle Scholar
  19. 19.
    Gabbiani F, Midtgaard J, Knopfel T. Synaptic integration in a model of cerebellar granule cells. J Neurophysiol 1994; 72: 999–1009.PubMedGoogle Scholar
  20. 20.
    D’Angelo E, Nieus T, Maffei A, Armano S, Rossi P, Taglietti V, Fontana A, Naldi G. Theta-frequency bursting and resonance in cerebellar granule cells: experimental evidence and modeling of a slow K+-dependent mechanism. J Neurosci 2001; 21: 759–770.PubMedGoogle Scholar
  21. 21.
    Hockberger PE, Tseng H-Y, Connor JA. Immunocytochemical and electrophysiological differentiation of rat cerebellar granule cells in explant cultures. J Neurosci 1987; 7: 1370–1383.PubMedGoogle Scholar
  22. 22.
    Robello M, Carignani C, Marchetti C. A transient voltagedependent outward current in cultured cerebellar granule neurons. Biosci Rep 1989; 9: 451–457.PubMedCrossRefGoogle Scholar
  23. 23.
    Cull-Candy SG, Marshall CG, Ogden D. Voltage-activated membrane currents in rat cerebellar granule neurons. J Physiol 1989; 414: 179–199.PubMedGoogle Scholar
  24. 24.
    Jalonen T, Johansson S, Holopainen I, Oja SS, Arhem P. Singlechannel and whole-cell currents in rat cerebellar granule cells. Brain Res 1990; 535: 33–38.PubMedCrossRefGoogle Scholar
  25. 25.
    Carignani C, Robello M, Marchetti C, Maga L. A transient outward current dependent on external calcium in rat cerebellar granule cells. J Membrane Biol 1991; 122: 259–265.CrossRefGoogle Scholar
  26. 26.
    Bardoni R, Belluzzi O. Kinetic study and numerical reconstruction of A-type current in granule cells of rat cerebellar slices. J Neurophysiol 1993; 69: 2222–2231.PubMedGoogle Scholar
  27. 27.
    Watkins CS, Mathie A. Modulation of the gating of the transient outward potassium current of rat isolated cerebellar granule neurons by lanthanum. Pfliigers Archiv/Eur J Physiol 1994; 428: 209–216.CrossRefGoogle Scholar
  28. 28.
    Zegarramoran O, Moran O. Properties of the transient potassium currents in cerebellar granule cells. Exp Brain Res 1994; 98: 298–304.Google Scholar
  29. 29.
    Jones G, Boyd DF, Yeung SY, Mathie A. Inhibition of delayed rectiner K+ conductance in cultured rat cerebellar granule neurons by activation of calcium-permeable AMPA receptors. Eur JNeurosci 2000; 12: 935–944.CrossRefGoogle Scholar
  30. 30.
    Watkins CS, Mathie A. Effect on K+ currents in rat cerebellar granule neurones of a membrane-permeable analogue of the calcium chelator BAPTA. Brit J Pharmacol 1996; 118: 1772–1778.Google Scholar
  31. 31.
    Chung YH, Shin CM, Kim MJ, Lee BK, Cha CI. Immunohistochemical study on the distribution of six members of the Kvl channel subunits in the rat cerebellum. Brain Res 2001; 895: 173–177.PubMedCrossRefGoogle Scholar
  32. 32.
    Kues WA, Wunder F. Heterogeneous expression patterns of mammalian potassium channel genes in developing and adult rat brain. Eur JNeurosci 1992; 4: 1296–1308.CrossRefGoogle Scholar
  33. 33.
    Sheng M, Tsaur ML, Jan YN, Jan LY. Contrasting subcellular localization of the Kv1.2 K+ channel subunit in different neurons of rat brain. J Neurosci 1994; 14: 2408–2417.PubMedGoogle Scholar
  34. 34.
    Veh RW, Lichtinghagen R, Sewing S, Wunder F, Grumbach 1M, Pongs O. Immunohistochemical localization of 5 members of the Kv1 channel subunits—contrasting subcellular locations and neuron-specific co-localizations in rat brain. Eur J Neurosci 1995; 7: 2189–2205.PubMedCrossRefGoogle Scholar
  35. 35.
    Shibata R, Nakahira K, Shibasaki K, Wakazono Y, Imoto K, Ikenaka K. A-type K+ current mediated by the Kv4 channel regulates the generation of action potential in developing cerebellar granule cells. J Neurosci 2000; 20: 4145–4155.PubMedGoogle Scholar
  36. 36.
    Drewe JA, Verma S, Frech G, Joho RH. Distinct spatial and temporal expression patterns of K+ channel messenger RNAs from different subfamilies. J Neurosci 1992; 12: 538–548.PubMedGoogle Scholar
  37. 37.
    VermaKurvari S, Border B, Joho RH. Regional and cellular expression patterns of four K+ channel mRNAs in the adult rat brain. Mol Brain Res 1997; 46: 54–62.CrossRefGoogle Scholar
  38. 38.
    Chung YH, Shin CM, Kim MJ, Lee BK, Cha CI. Age-related changes in the distribution of Kv1. 1 and Kv1.2 channel subunits in the rat cerebellum. Brain Res 2001; 897: 193–198.PubMedCrossRefGoogle Scholar
  39. 39.
    Wang H, Kunkel DD, Schwartzkroin PA, Tempel BL. Localization of Kv1.1 and Kv1.2 K-channel proteins, to synaptic terminals, somata and dendrites in the mouse brain. J Neurosci 1994; 14: 4588–4599.PubMedGoogle Scholar
  40. 40.
    Southan AP, Robertson B. Patch-clamp recordings from cerebellar basket cell bodies and their presynaptic terminals reveal an asymmetric distribution of voltage-gated potassium channels. J Neurosci 1998; 18: 948–955.PubMedGoogle Scholar
  41. 41.
    Leicher T, Bahring R, Isbrandt D, Pongs O. Coexpression of the KCNA3B gene product with Kv1.5 leads to a novel A-type potassium. J Biol Chem 1998; 273: 35095–35101.PubMedCrossRefGoogle Scholar
  42. 42.
    Downen M, Belkowski S, Knowles H, Cardillo M, Prystowsky MB. Developmental expression of voltage-gated potassium channel beta subunits. Dev Brain Res 1999; 117: 71–80.CrossRefGoogle Scholar
  43. 43.
    Rettig 1, Heinemann SH, Wunder F, Lorra C, Wittka R, Dolly O, Pongs O. Inactivation properties of voltage-gated K+ channels altered by the presence of beta-subunit. Nature 1994; 369: 289–294.PubMedCrossRefGoogle Scholar
  44. 44.
    Rhodes KJ, Monaghan MM, Barrezueta NX, Nawoschik S, BekeleArcuri Z, Matos MF, Nakahira K, Schechter LE, Trimmer JS. Voltage-gated K+ channel beta subunits: expression and distribution of Kv beta 1 and Kv beta 2 in adult rat brain. J Neurosci 1996; 16: 4846–4860.PubMedGoogle Scholar
  45. 45.
    Butler DM, Ono JK, Chang T, McCaman RE, Barish ME. Mouse brain potassium channel beta 1 subunit mRNA. Cloning and distribution during development. J Neurobiol 1998; 34: 135–150.PubMedCrossRefGoogle Scholar
  46. 46.
    Browne DL, Gancher ST, Nutt JG, Brunt ER, Smith EA, Kramer P, Litt M. Episodic ataxia/myokymia syndrome is associated with a point mutation in the human potassium channel gene, KCNAI. Nature Genetics 1994; 8: 136–140.PubMedCrossRefGoogle Scholar
  47. 47.
    Adelman JP, Bond CT, Pessia M, Maylie J. Episodic ataxia results from voltage-dependent potassium channels with altered functions. Neuron 1995; 15: 1449–1454.PubMedCrossRefGoogle Scholar
  48. 48.
    Hwang PM, Glatt CE, Bredt DS, Yellen G, Snyder SH. A novel K+ channel with unique localizations in mammalian brain—molecular-cloning and characterization. Neuron 1992; 8: 473–481.PubMedCrossRefGoogle Scholar
  49. 49.
    Fink M, Duprat F, Lesage F, Heurteaux C, Romey G, Barhanin J, Lazdunski M. A new K+ channel beta subunit to specifically enhance Kv2.2 (CDRK) expression. J Biol Chem 1996; 271: 26341–26348.PubMedCrossRefGoogle Scholar
  50. 50.
    Sekirnjak C, Martone ME, Weiser M, Deerinck T, Bueno E, Rudy B, Ellisman M. Subcellular localization of the K+ channel subunit Kv3.1b in selected rat CNS neurons. Brain Res 1997; 766: 173–187.PubMedCrossRefGoogle Scholar
  51. 51.
    Perney TM, Marshall J, Martin KA. Expression of the messenger RNAs for the Kv3.1 potassium channel gene in the adult and developing rat brain. J Neurophysiol 1992; 68: 756–766.PubMedGoogle Scholar
  52. 52.
    Weiser M, Demiera EVS, Kentros C, Moreno H, Franzen L, Hillman D, Baker H, Rudy B. Differential expression of shawrelated K+ channels in the rat central nervous system. J Neurosci 1994; 14: 949–972.PubMedGoogle Scholar
  53. 53.
    Shibata R, Wakazono Y, Nakahira K, Trimmer JS, Ikenaka K. Expression of Kv3.1 and Kv4.2 genes in developing cerebellar granule cells. Dev Neurosci 1999; 21: 87–93.PubMedCrossRefGoogle Scholar
  54. 54.
    Sabatini BL, Regehr WG. Control of neurotransmitter release by presynaptic waveform at the granule cell to Purkinje cell synapse. J Neurosci 1997; 17: 3425–3435.PubMedGoogle Scholar
  55. 55.
    Espinosa F, McMahon A, Chan E, Wang S, Ho CS, Heintz N, Joho RH. Alcohol hypersensitivity, increased locomotion, and spontaneous myoclonus in mice lacking the potassium channels Kv3.1 and Kv3.3. J Neurosci 2001; 21: 6657–6665.PubMedGoogle Scholar
  56. 56.
    Tsaur ML, Chou CC, Shih YH, Wang HL. Cloning, expression and CNS distribution of Kv4.3, an A-type K+ channel alpha subunit. FEBS Lett 1997; 400: 215–220.PubMedCrossRefGoogle Scholar
  57. 57.
    Serodio P, Rudy B. Differential expression of Kv4 K+ channel subunits mediating subthreshold transient K+ (A-type) currents in rat brain. J Neurophysiol 1998; 79: 1081–1091.PubMedGoogle Scholar
  58. 58.
    An WF, Bowlby MR, Bett M, Cao J, Ling HP, Mendoza G, Hinson JW, Mattsson KI, Strassle BW, Trimmer JS, Rhodes KJ. Modulation of A-type potassium channels by a family of calcium sensors. Nature 2000; 403: 553–556.PubMedCrossRefGoogle Scholar
  59. 59.
    Holmqvist MH, Cao J, Hernandez-Pineda R, Jacobson MD, Carroll KI, Sung MA, Betty M, Ge P, Gilbride KJ, Brown ME, Jurman ME, Lawson D, Silos-Santiago I, Xie Y, Covarrubias M, Rhodes KJ, Distefano PS, An WF. Elimination of fast inactivation in Kv4 A-type potassium channels by an auxiliary subunit domain. Proc Natl Acad Sci USA 2002; 99: 1035–1040.PubMedCrossRefGoogle Scholar
  60. 60.
    Hugnot JP, Salinas M, Lesage F, Guillemare E, deWeille J, Heurteaux C, Mattei MG, Lazdunski M. Kv8.1, a new neuronal potassium channel subunit with specific inhibitory properties towards shab and shaw channels. EMBO J 1996; 15: 3322–3331.PubMedGoogle Scholar
  61. 61.
    Castellano A, Chiara MD, Mellstrom B, Lopez-Barneo J. Identification and functional characterization of a K+ channel alphasubunit with regulatory properties specific to brain. J Neurosci 1997; 17: 4652–4661.PubMedGoogle Scholar
  62. 62.
    Salinas M, deWeille J, Guillemare E, Lazdunski M, Hugnot JP. Modes of regulation of shab K+ channel activity by the Kv8.1 subunit. J Biol Chem 1997; 272: 8774–8780.PubMedCrossRefGoogle Scholar
  63. 63.
    Salinas M, Duprat F, Heurteaux C, Hugnot JP, Lazdunski M. New modulatory alpha subunits for mammalian shab K+ channels. J Biol Chem 1997; 272: 24371–24379.PubMedCrossRefGoogle Scholar
  64. 64.
    Stocker M, Kerschensteiner D. Cloning and tissue distribution of two new potassium channel alpha-subunits from rat brain. Biochem Biophys Res Commun 1998; 248: 927–934.PubMedCrossRefGoogle Scholar
  65. 65.
    Kramer JW, Post MA, Brown AM, Kirsch GE. Modulation of potassium channel gating by coexpression of Kv2.1 with regulatory Kv5.1 or Kv6.1 alpha-subunits. Am J Physiol: Cell Physiol 1998; 43: C1501-C1510.Google Scholar
  66. 66.
    Huang XV, Morielli AD, Peralta EG. Tyrosine kinase-dependent suppression of a potassium channel by the G protein-coupled ml muscarinic acetylcholine receptor. Cell 1993; 75: 1145–1156.PubMedCrossRefGoogle Scholar
  67. 67.
    Jonas EA, Kaczmarek LK. Regulation of potassium channels by protein kinases. Curr Opin Neurobiol 1996; 6: 318–323.PubMedCrossRefGoogle Scholar
  68. 68.
    Saganich MJ, Machado E, Rudy B. Differential expression of genes encoding subthreshold-operating voltage-gated K+ channels in brain. J Neurosci 2001; 21: 4609–4624.PubMedGoogle Scholar
  69. 69.
    Ludwig J, Weseloh R, Karschin C, Liu Q, Netzer R, Engeland B, Stansfeld C, Pongs O. Cloning and functional expression of rat eag2, a new member of the ether-a-go-go family of potassium channels and comparison of its distribution with that of eagl. Mol Cell Neurosci 2000; 16: 59–70.PubMedCrossRefGoogle Scholar
  70. 70.
    Hoshi N, Takahashi H, Shahidullah M, Yokoyama S, Higashida H. KCR1, a membrane protein that facilitates functional expression of non-inactivating K+ currents associates with rat eag voltage-dependent K+ channels. J Biol Chem 1998; 273: 23080–23085.PubMedCrossRefGoogle Scholar
  71. 71.
    Watkins CS, Mathie A. A non-inactivating K+ current sensitive to muscarinic receptor activation in rat cultured cerebellar granule neurons. J Physiol 1996; 491:401–412.PubMedGoogle Scholar
  72. 72.
    Martion NV. Does r-eag contribute to the M current? Trends in Neurosci 1997; 20: 243–244.CrossRefGoogle Scholar
  73. 73.
    Mathie A, Watkins CS. Is EAG the answer to the M current? Trends in Neurosci 1997; 20: 14.CrossRefGoogle Scholar
  74. 74.
    Wang HS, Pan ZM, Shi WM, Brown BS, Wymore RS, Cohen IS, Dixon JE, McKinnon D. KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science 1998; 282: 1890–1893.PubMedCrossRefGoogle Scholar
  75. 75.
    Tinel N, Lauritzen I, Chouabe C, Lazdunski M, Borsotto M. The KCNQ2 potassium channel splice variants, function and developmental expression. Brain localization and comparison with KCNQ3. FEBS Lett 1998; 438: 171–176.PubMedCrossRefGoogle Scholar
  76. 76.
    Kharkovets T, Hardelin J-p, Safieddine S, Schweizer M, El-Amraoui A, Petit C, Jentsch TJ. KCNQ4 a K channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathway. Proc Natl Acad Sci USA 2000; 97: 4333–4338.PubMedCrossRefGoogle Scholar
  77. 77.
    Lerche C, Scherer CR, Seebohm G, Derst C, Wei AD, Busch AE, Steinmeyer K. Molecular cloning and functional expression of KCNQ5, a potassium channel subunit that may contribute to neuronal M current diversity. J Biol Chem 2000; 275: 22395–22400.PubMedCrossRefGoogle Scholar
  78. 78.
    Schroeder BC, Hechenberger M, Weinreich F, Kubisch C, Jentsch TJ. KCNQ5, a novel potassium channel broadly expressed in brain, mediates M-type currents. J Biol Chem 2000; 275: 24089–24095.PubMedCrossRefGoogle Scholar
  79. 79.
    Fagni L, Bossu JL, Bockaert J. Activation of a large conductance Ca2+ dependent K+ channel by stimulation of glutamate phosphoinositide-coupled receptors in cultured cerebellar granule cells. Eur J Neurosci 1991; 3: 778–789.PubMedCrossRefGoogle Scholar
  80. 80.
    Chavis P, Ango F, Michel JM, Bockaert J, Fagni L. Modulation of big K+ channel activity by ryanodine receptors and L-type Ca2+ channels in neurons. Eur J Neurosci 1998; 10: 2322–2327.PubMedCrossRefGoogle Scholar
  81. 81.
    Adelman JP, Shen KZ, Kavanaugh MP, Warren RA, Wu YN, Lagrutta A, Bond CT, North RA. Calcium-activated potassium channels expressed from cloned complementary DNAs. Neuron 1992; 9: 209–216.PubMedCrossRefGoogle Scholar
  82. 82.
    TsengCrank J, Foster CD, Krause JD, Mertz R, Godinot N, Dichiara TJ, Reinhart PH. Cloning, expression and distribution of functionally distinct Ca2+-activated K+ channel isoforms from human brain. Neuron 1994; 13: 1315–1330.CrossRefGoogle Scholar
  83. 83.
    Knaus HG, Schwarzer C, Koch ROA, Eberhart A, Kaczorowski GJ, Glossmann H, Wunder F, Pongs O, Garcia ML, Sperk G. Distribution of high-conductance Ca2+-activated K+ channels in rat brain: targeting to axons and nerve terminals. J Neurosci 1996; 16: 955–963.PubMedGoogle Scholar
  84. 84.
    Chang CP, Dworetzky SI, Wang JC, Goldstein ME. Differential expression of the alpha and beta subuits of the large-conductance calcium-activated potassium channel. Implication for channel diversity. Mol Brain Res 1997; 45: 33–40.PubMedCrossRefGoogle Scholar
  85. 85.
    Muller YL, Reitstetter R, Yool AJ. Regulation of Ca2+-dependent K+ channel expression in rat cerebellum during postnatal development. J Neurosci 1998; 18: 16–25.PubMedGoogle Scholar
  86. 86.
    Stocker M, Pedarzani P. Differential distribution of three Ca2+activated K+ channel subunits, SK1, SK2, and SK3, in the adult rat central nervous system. Mol Cell Neurosci 2000; 15: 476–493.PubMedCrossRefGoogle Scholar
  87. 87.
    Joiner WI, Wang L-Y, Tang MD, Kaczmarek LK. hSK4, a member of a novel subfamily of calcium-activated potassium channels. Proc Natl Acad Sci USA 1997; 94: 11013–11018.PubMedCrossRefGoogle Scholar
  88. 88.
    Kofuji P, Hofer M, Millen KJ, Millonig JH, Davidson N, Lester HA, Hatten ME. Functional analysis of the weaver mutant GIRK2 K+ channel and rescue of weaver granule cells. Neuron 1996; 16:941–952.PubMedCrossRefGoogle Scholar
  89. 89.
    Surmeier JD, Mermelstein PG, Goldowitz D. The weaver mutation of GIRK2 results in a loss of inwardly-rectifying K+ current in cerebellar granule cells. Proc Natl Acad Sci USA 1996; 93: 11191–11195.PubMedCrossRefGoogle Scholar
  90. 90.
    Slesinger PA, Stoffel M, Jan YN, Jan LY. Defective GABAB receptor-activated inwardly-rectifying K+ currents in cerebellar granule cells isolated from weaver and Girk2 null mutant mice. Proc Natl Acad Sci USA 1997; 94: 12210–12217.PubMedCrossRefGoogle Scholar
  91. 91.
    Liesi P, Stewart RR, Wright JM. Involvement of GIRK2 in postnatal development of the weaver cerebellum. J Neurosci Res 2000; 60: 164–173.PubMedCrossRefGoogle Scholar
  92. 92.
    Mjaatvedt AE, Cabin DE, Cole SE, Long LJ, Breitweiser GE, Reeves RH. Assessment of a mutation in the H5 domain of GIRK2 as a candidate for the weaver mutation. Genome Res 1995; 5: 453–463.PubMedCrossRefGoogle Scholar
  93. 93.
    Rossi P, De Filippi G, Armano S, Taglietti V, D’Angelo E. The weaver mutation causes a loss of inward-rectifier current regulation in premigratory granule cell of the mouse cerebellum. J Neurosci 1998; 18: 3537–3547.PubMedGoogle Scholar
  94. 94.
    Dixon AK, Gubitz AK, Ashford MLJ, Richardson PJ, Freeman TC. Distribution of the mRNA encoding the inwardly rectifying K+ channel, BIRI in rat tissues. FEBS Lett 1995; 374: 135–140.PubMedCrossRefGoogle Scholar
  95. 95.
    Liao YJ, Jan YN, Jan LY. Heteromultimerization of G-protein inwardly rectifying K+ channel proteins GIRK1 and GIRK2 and their altered expression in weaver brain. J Neurosci 1996; 16: 7137–7150.PubMedGoogle Scholar
  96. 96.
    Karschin C, Dissmann E, Stuhmer W, Karschin A. IRK(1–3) and GIRK(1–4) inwardly rectifying K+ channel mRNAs are differentially expressed in the adult rat brain. J Neurosci 1996; 16: 3559–3570.PubMedGoogle Scholar
  97. 97.
    Karschin C, Karschin A. Ontogeny of gene expression of Kir channel subunits in the rat. Mol Cell Neurosci 1997; 10: 131–148.PubMedCrossRefGoogle Scholar
  98. 98.
    Lauritzen I, De Weille JD, Adelbrecht C, Lesage F, Murer MG, Raisman-Vozari R, Lazdunski M. Comparative expression of the inward-rectifier K+ channel GIRK2 in the cerebellum of normal and weaver mutant mice. Brain Res 1997; 753: 8–17.PubMedCrossRefGoogle Scholar
  99. 99.
    Miyashita T, Kubo Y. Localization and developmental changes of the expression of two inward rectifying K+-channel proteins in the rat brain. Brain Res 1997; 750: 251–263.PubMedCrossRefGoogle Scholar
  100. 100.
    Murer G, Adelbrecht C, Lauritzen I, Lesage F, Lazdunski M, Agid Y, Raisman-Vorazi R. An immunocytochemical study on the distribution of two G-protein-gated inward rectifier potassium channels (GIRK2 and GIRK4) in the adult rat brain. Neurosci 1997; 80: 345–357.CrossRefGoogle Scholar
  101. 101.
    Navarro B, Kennedy ME, Velimirovic B, Bhat D, Peterson AS, Clapham DE. Nonselective and Gβ-γ-insensitive weaver K+ channels. Science 1996; 272: 1950–1953.PubMedCrossRefGoogle Scholar
  102. 102.
    Horio Y, Morishige K, Takahashi N, Kurachi Y. Differential distribution of classical inwardly rectifying potassium channel mRNAs in the brain: Comparison of IRK2 with IRK1 and IRK3. FEBS Lett 1996; 379: 239–243.PubMedCrossRefGoogle Scholar
  103. 103.
    Topert C, Doring F, Wischmeyer E, Karschin C, Brockhaus J, Ballanyi K, Derst C, Karschin A. Kir2.4: A novel K+ inward rectifier channel associated with motoneurons of cranial nerve nuclei. J Neurosci 1998; 18: 4096–4105.PubMedGoogle Scholar
  104. 104.
    Karschin C, Ecke C, Ashcroft FM, Karschin A. Overlapping distribution of KATP channel-forming Kir6.2 subunit and the sulphonylurea receptor SUR1 in rodent brain. FEBS Lett 1997; 401: 59–64.PubMedCrossRefGoogle Scholar
  105. 105.
    Thomzig A, Wenzel M, Karschin C, Eaton MJ, Skatchkov SN, Karschin A, Veh RW. Kir6.1 is the principal pore-forming subunit of astrocyte but not neuronal plasma membrane K-ATP channels. Mol Cell Neurosci 2001; 18: 671–690.PubMedCrossRefGoogle Scholar
  106. 106.
    Pessia M, Imbrici P, D’Adamo C, Salvatore L, Tucker SJ. Differential pH sensitivity of Kir4.1 and Kir4.2 potassium channels and their modulation by heteropolymerisation with Kir5.1. J Physiol 2001; 532: 359–367.PubMedCrossRefGoogle Scholar
  107. 107.
    Slesinger PA, Patil N, Liao YJ, Jan YN, Jan LY, Cox DR. Functional effects of the mouse weaver mutation on G-protein-gated inwardly rectifying K+ channels. Neuron 1996; 16: 321–331PubMedCrossRefGoogle Scholar
  108. 108.
    Reeves RH, Crowley MR, Lorenzon N, Pavan WJ, Smeyne RJ, Goldowitz D. The mouse neurological mutant weaver maps within the region of chromosome-16 that is homologous to human chromosome-21. Genomics 1989; 5: 522–526.PubMedCrossRefGoogle Scholar
  109. 109.
    Doyle DA, Cabral JM, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chiat BT, MacKinnon R. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 1998; 280: 69–77.PubMedCrossRefGoogle Scholar
  110. 110.
    Boyd DF, Mathie A. Inhibition of the potassium current IKso, in cerebellar granule cells, by the inhibitors of MEK1 activation, PD 98059 and U 0126. Neuropharmacol 2002; 42: 221–228.CrossRefGoogle Scholar
  111. 111.
    Boyd DF, Millar JA, Watkins CS, Mathie A. The role of Ca2+ stores in the muscarinic inhibition of the K+ current IKso in neonatal rat cerebellar granule cells. J Physiol 2000; 529: 321–331.PubMedCrossRefGoogle Scholar
  112. 112.
    Millar JA, Barratt L, Southan AP, Page KM, Fyffe REW, Robertson B, Mathie A. A functional role for the two-pore domain potassium channel, TASK-1, in cerebellar granule neurons. Proc Natl Acad Sci USA 2000; 97: 3614–3618PubMedCrossRefGoogle Scholar
  113. 113.
    Maingret F, Patel AJ, Lazdunski M, Honore E. The endocannabinoid anandamide is a direct and selective blocker of the background K+ channel TASK-1. EMBO J 2001; 20: 47–54.PubMedCrossRefGoogle Scholar
  114. 114.
    Lauritzen I, Blondeau N, Heurteaux C, Widmann C, Romey G, Lazdunski M. Polyunsaturated fatty acids are potent neuroprotectors. EMBO J 2000; 19: 1784–1793PubMedCrossRefGoogle Scholar
  115. 115.
    Lesage F, Lazdunski M. Molecular and functional properties of two-pore-domain potassium channels. Am J Physiol Renal Physiol 2000; 279: F793-F801.PubMedGoogle Scholar
  116. 116.
    Patel AJ, Honore E. Properties and modulation of mammalian 2P domain K+ channels. Trends Neurosci 2001; 24: 339–346.PubMedCrossRefGoogle Scholar
  117. 117.
    Lesage F, Guillemare E, Fink M, Duprat F, Lazdunski M, Romey G, Barhanin J. TWIK-1, a ubiquitous human weakly inward rectifYing K+ channel with a novel structure. EMBO J 1996; 15: 1004–1011.PubMedGoogle Scholar
  118. 118.
    Chavez RA, Gray AT, Zhao BB, Kindler CH, Mazurek MJ, Mehta Y, Forsayeth JR, Yost CS. TWIK-2, a new weak inward rectifying member of the tandem pore domain potassium channel family. J Biol Chem 1999; 274: 7887–7892.PubMedCrossRefGoogle Scholar
  119. 119.
    Patel AJ, Maingret F, Magnone V, Fosset M, Lazdunski M, Honore E. TWIK-2, an inactivating 2P domain K+ channel. J Biol Chem 2000; 275: 28722–28730PubMedCrossRefGoogle Scholar
  120. 120.
    Reyes R, Duprat F, Lesage F, Fink M, Salinas M, Farman N, Lazdunski M. Cloning and expression of a novel pH-sensitive two pore domain K+ channel from human kidney. J Biol Chem 1998; 273: 30863–30869.PubMedCrossRefGoogle Scholar
  121. 121.
    Kim Y, Bang H, Kim D. TASK-3, a new member of the tandem pore K+ channel family. J Biol Chem 2000; 275: 9340–9347.PubMedCrossRefGoogle Scholar
  122. 122.
    Rajan S, Wischmeyer E, Liu GX, Preisig-Muller R, Daut J, Karschin A, Derst C. TASK-3, a novel tandem pore domain acid-sensitive K+ channel. J Biol Chem 2000; 275: 16650–16657.PubMedCrossRefGoogle Scholar
  123. 123.
    Meadows HJ, Randall AD. Functional characterization of human TASK-3, an acid-sensitive two-pore domain potassium channel. Neuropharmacol 2001; 40: 551–559.CrossRefGoogle Scholar
  124. 124.
    Decher N, Maier M, Dittrich W, Gassenhuber J, Bruggemann A, Busch AE, Steinmeyer K. Characterization of TASK-4, a novel member of the pH-sensitive, two-pore domain potassium channel family. FEBS Lett 2001; 492: 84–89PubMedCrossRefGoogle Scholar
  125. 125.
    Ashmole I, Goodwin PA, Stanfield PR. TASK-5 a novel member of the tandem pore K+ channel family. Pftugers Archiv 2001; 442: 828–833.CrossRefGoogle Scholar
  126. 126.
    Kim D, Gnatenco C. TASK-5, a new member of the tandempore K+ channel family. Biochem Biophys Res Commun 2001; 284: 923–930.PubMedCrossRefGoogle Scholar
  127. 127.
    Vega-Saenz De Miera E, Lau DHP, Zhadina M, Pountney D, Coetzee WA, Rudy B. KT3.2 and KT3.3, two novel human twopore K+ channels closely related to TASK-I. J Neurophysiol 2001; 86: 130–142.Google Scholar
  128. 128.
    Karschin C, Wischmeyer E, Preisig-Muller R, Rajan S, Derst C, Grzeschik K-H, Daut J, Karschin A. Expression pattern in brain of TASK-I, TASK-3 and a tandem pore domain K+ channel subunit, TASK-5, associated with the central auditory nervous system. Mol Cell Neurosci 2001; 18: 632–648.PubMedCrossRefGoogle Scholar
  129. 129.
    Duprat F, Lesage F, Fink M, Reyes R, Heurteaux C, Lazdunski M. TASK, a human background K+ channel to sense external pH variations near physiological pH. EMBO J 1997; 16: 5464–5471.PubMedCrossRefGoogle Scholar
  130. 130.
    Girard C, Duprat F, Terrenoire C, Tinel N, Fosset M, Romey G, Lazdunski M, Lesage F. Genomic and functional characteristics of novel human pancreatic 2P domain K+ channels. Biochem Biophys Res Commun 2001; 282: 249–256.PubMedCrossRefGoogle Scholar
  131. 131.
    Fink M, Duprat F, Lesage F, Reyes R, Romey G, Heurteaux C, Lazdunski M. Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel. EMBO J 1996; 15: 6854–6862.PubMedGoogle Scholar
  132. 132.
    Fink M, Lesage F, Duprat F, Heurteaux C, Reyes R, Fosset M, Lazdunski M. A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids. EMBO J 1998; 17: 3297–3308.PubMedCrossRefGoogle Scholar
  133. 133.
    Bang H, Kim Y, Kim D. TREK-2, a new member of the mechanosensitive tandem-pore K+ channel family. J Biol Chem 2000; 275:17412–17419PubMedCrossRefGoogle Scholar
  134. 134.
    Rajan S, Wischmeyer E, Karschin C, Preisig-Muller R, Grzeschik KH, Daut J, Karschin A, Derst C. THIK-l and THIK-2, a novel subfamily of tandem pore domain K+ channels. J Biol Chem 2001; 276: 7302–7311.PubMedCrossRefGoogle Scholar
  135. 135.
    Bushell T, Clarke C, Mathie A, Robertson B. Pharmacological characterization of a non-inactivating outward current observed in mouse cerebellar Purkinje neurones. Br J Pharmacol 2002; 135: 705–712.PubMedCrossRefGoogle Scholar
  136. 136.
    Salinas M, Reyes R, Lesage F, Fosset M, Heurteaux C, Romey G, Lazdunski M. Cloning of a new mouse two-P domain channel subunit and a human homologue with a unique pore structure. J Biol Chem 1999; 274: 11751–11760.PubMedCrossRefGoogle Scholar
  137. 137.
    Talley EM, Solorzano G, Lei Q, Kim D, Bayliss DA. CNS distribution of members of the two-pore-domain (KCNK) potassium channel family. J Neurosci 2001; 21: 7491–7505.PubMedGoogle Scholar
  138. 138.
    Medhurst AD, Rennie G, Chapman CG, Meadows H, Duckworth MD, Kelsell RE, Gloger II, Pangalos MN. Distribution analysis of human two pore domain potassium channels in tissues of the central nervous system and periphery. Brain Res Mol Brain Res 2001; 86: 101–114PubMedCrossRefGoogle Scholar
  139. 139.
    Brickley SG, Revilla V, Cull-Candy SG, Wisden W, Farrant M. Adaptive regulation of neuronal excitability by a voltageindependent potassium conductance. Nature 2001; 409: 88–92.PubMedCrossRefGoogle Scholar
  140. 140.
    Hervieu GJ, Cluderay JE, Gray CW, Green PJ, Ranson JL, Randall AD, Meadows HJ. Distribution and expression of TREK-I, a two-pore-domain potassium channel, in the adult rat CNS. Neurosci 2001; 103: 899–919.CrossRefGoogle Scholar
  141. 141.
    Gu W, Schlichthorl G, Hirsch JR, Engels H, Karschin C, Karschin A, Derst C, Steinlein OK, Daut J. Expression pattern and functional characteristics of two novel splice variants of the two-pore domain potassium channel TREK-2. J Physiol 2002; 539:657–668.PubMedCrossRefGoogle Scholar
  142. 142.
    Han J, Truell J, Gnatenco C, Kim D. Several tandem-pore K+ channels contribute to the background current in cerebellar granule neurons. Biophys J 2002; 82: 636a.CrossRefGoogle Scholar
  143. 143.
    Czirjak G, Enyedi P. Formation of functional heterodimers between the TASK-1 and TASK-3 two-pore domain potassium channel subunits. J Biol Chem 2002; 277: 5426–5432.PubMedCrossRefGoogle Scholar
  144. 144.
    GoldmanWohl DS, Chan E, Baird D, Heintz N. Kv3.3B — A novel shaw type potassium channel expressed in terminally differentiated cerebellar Purkinje cells and deep cerebellar nuclei. J Neurosci 1994; 14: 511–522.Google Scholar
  145. 145.
    McNamara NMC, Averill S, Wilkin GP, Dolly JO, Priestley N. Ultrastructural localization of a voltage-gated K+ channel alpha subunit (Kv1.2) in the rat cerebellum. Eur J Neurosci 1996; 8: 688–699.PubMedCrossRefGoogle Scholar
  146. 146.
    Shu-Cheng C, Ehrhard P, Goldowitz D, Smeyne RJ. Developmental expression of the GIRK family of inward rectif Ying potassium channels: implications for abnormalities in the weaver mutant mouse. Brain Res 1997; 778: 251–264.CrossRefGoogle Scholar
  147. 147.
    Kindler CH, Pietruck C, Yost CS, Sampson ER, Gray AT. Localization of the tandem pore domain K+ channel TASK-1 in the rat central nervous system. Brain Res Mol Brain Res 2000; 80: 99–108PubMedCrossRefGoogle Scholar
  148. 148.
    Talley EM, Lei QB, Sirois JE, Bayliss DA. TASK-1, a two-pore domain K+ channel, is modulated by multiple neurotransmitters in motoneurons. Neuron 2000; 25: 399–410.PubMedCrossRefGoogle Scholar
  149. 149.
    Gabriel A, Abdallah M, Yost CS, Winegar BD, Kindler CH. Localization of the tandem pore domain K+ channel KCNK5 (TASK-2) in the rat central nervous system. Mol Brain Res 2002; 98: 153–163.PubMedCrossRefGoogle Scholar

Copyright information

© Taylor & Francis 2003

Authors and Affiliations

  • Alistair Mathie
    • 1
  • Catherine E. Clarke
    • 1
  • Kishani M. Ranatunga
    • 1
  • Emma L. Veale
    • 1
  1. 1.Biophysics Section, Blackett Laboratory, Department of Biological SciencesImperial College of Science Technology and MedicineLondonUK

Personalised recommendations