Structure and Function of Receptor-Mediated Chloride Channels in the Central Nervous System

  • Kinya Kuriyama
  • Masaaki Hirouchi
Part of the Endocrinology and Metabolism book series (EAM, volume 6)


The central nervous system (CNS) Cl channels are typical anion channels, which can be classified as receptor-mediated, voltage-sensitive, and calcium-dependent Cl channels.1 The receptors for GABA and glycine, major inhibitory neurotransmitters in the CNS, contain receptor-mediated Cl channels that open upon activation of the receptors, inducing the transduction of an inhibitory signal such as an inhibitory postsynaptic potential (IPSP).


GABAA Receptor Gaba Receptor Glycine Receptor GABAA Receptor Subunit Inhibitory Postsynaptic Potential 
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  1. 1.
    Eldefrawi AT, Eldefrawi ME. Receptors for y-aminobutyric acid and voltage-dependent chloride channels as targets for drugs and toxicants. FASEB J 1987; 1:262–271.PubMedGoogle Scholar
  2. 2.
    Strange PG. The structure and mechanism of neurotransmitter receptors. Biochem J 1988; 249:309–318.PubMedGoogle Scholar
  3. 3.
    Braestrup C, Nielsen M, Homore T, Jensen LH, Petersen EN. Benzodiazepine receptor ligands with positive and negative efficacy. Neuropharmacology 1983; 22:1451–1458.PubMedCrossRefGoogle Scholar
  4. 4.
    Ticku MK. Benzodiazepine-GABA receptor-ionophore complex: Current concepts. Neuropharmacology 1983; 22:1459–1470.PubMedCrossRefGoogle Scholar
  5. 5.
    Taguchi J, Kuriyama K. Functional modulation of cerebral y-aminobutyric acidA receptor/benzodiazepine receptor/chloride ion channel complex with ethyl ß-carboline-3-carboxylate: Presence of independent binding site for ethyl ß-carboline-3-carboxylate. J Pharmacol Exp Ther 1990; 253:558–566.PubMedGoogle Scholar
  6. 6.
    Puia G, Santi M, Vicini S, Pritchett DB, Purdy RH, Paul SM, Seeburg PH, Costa E. Neurosteroids act on recombinant human GABAA receptors. Neuron 1990; 4:759–765.PubMedCrossRefGoogle Scholar
  7. 7.
    Majewska MD, Demirgoren S, Spivak CE, London ED. The neurosteroid dehydroepiandrosterone sulfate is an allosteric antagonist of the GABAA receptor. Brain Res 1990; 526:143–146.PubMedCrossRefGoogle Scholar
  8. 8.
    Schumacher M, McEwen BS. Steroid and barbiturate modulation of the GABAA receptor: Possible mechanisms. Mol Neurobiol 1989; 3:275–304.PubMedCrossRefGoogle Scholar
  9. 9.
    Burt DR, Kamatchi GL. GABAA receptor subtypes: From pharmacology to molecular biology. FASEB J 1991; 5:2916–2923.PubMedGoogle Scholar
  10. 10.
    Kuriyama K, Hirouchi M. Structure and function of y-aminobutyric acid (GABA) receptor: Current state and prospectives. Folia Pharmacol Japon 1989; 94:7–15.CrossRefGoogle Scholar
  11. 11.
    Schofield PR, Darlison MG, Fujita N, Burt DR, Stephenson FA, Rodriguez H, Rhee LM, Ramachandran J, Reale V, Glencorse TA, Seeburg PH, Barnard EA. Sequence and functional expression of the GABAA receptor shows a ligand-gated receptor super-family. Nature 1987; 328:221–227.PubMedCrossRefGoogle Scholar
  12. 12.
    Pritchett DB, Sontheimer H, Shivers BD, Ymer S, Kettenmann H, Schofield PR, Seeburg PH. Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology. Nature 1989; 338:582–585.PubMedCrossRefGoogle Scholar
  13. 13.
    Shivers BD, Killisch I, Sprengel R, Sontheimer H, Kohler M, Schofield PR, Seeburg PH. Two novel GABAA receptor subunits exist in distinct neuronal subpopulations. Neuron 1989; 3:327–337.PubMedCrossRefGoogle Scholar
  14. 14.
    Cutting GR, Lu L, O’Hara BF, Kasch LM, Montrose-Rafizadeh C, Donovan DM, Shimada S, Antonarakis SE, Guggino WB, Uhl GR, Kazazian HH. Jr Cloning of the y-aminobutyric acid (GAB A) p! cDNA: A GAB A receptor subunit highly expressed in the retina. Proc Natl Acad Sei USA 1991; 88:2673–2677.CrossRefGoogle Scholar
  15. 15.
    Levitan ES, Schofield PR, Burt DR, Rhee LM, Wisden W, Kohler M, Fujita N, Rodriguez HF, Stephenson A, Darlison MG, Barnard EA, Seeburg PH. Structure and functional basis for GABAA receptor heterogeneity. Nature 1988; 335:76–79.PubMedCrossRefGoogle Scholar
  16. 16.
    Ymer S, Schofield PR, Draguhn A, Werner P, Kohler M, Seeburg PH. GAB A A receptor ß subunit heterogeneity: Functional expression of cloned cDNAs. EMBO J 1989; 8:1665–1670.PubMedGoogle Scholar
  17. 17.
    Pritchett DB, Luddens H, Seeburg PH. Type I and type II GABAA/ benzodiazepine receptors produced in transfected cells. Science 1989; 245:1389–1392.PubMedCrossRefGoogle Scholar
  18. 18.
    Pritchett DB, Seeburg PH. y-aminobutyric acidA receptor a5-subunit creates novel type II benzodiazepine receptor pharmacology. J Neurochem 1990; 54:1802–1804.PubMedCrossRefGoogle Scholar
  19. 19.
    Luddens H, Pritchett DB, Kohier M, Killisch I, Keinanen K, Monyer H, Sprengel R, Seeburg PH. Cerebellar GABAA receptor selective for a behavioral alcohol antagonist. Nature 1990; 346:648–651.PubMedCrossRefGoogle Scholar
  20. 20.
    Sigel E, Baur R, Trübe G, Möhler H, Malherbe P. The effect of subunit composition of rat GABAA receptors on channel function. Neuron 1990; 5:703–711.PubMedCrossRefGoogle Scholar
  21. 21.
    Heuschneider G, Schwartz RD. cAMP and forskolin decrease y-aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes. Proc Natl Acad Sei USA 1989; 86:2938–2942.CrossRefGoogle Scholar
  22. 22.
    Kirkness EF, Bovenkerk CF, Ueda T, Turner AJ. Phosphorylation of y-aminobutyrate (GABA)/benzodiazepine receptors by cyclic AMP-dependent protein kinase. Biochem J 1989; 259:613–616.PubMedGoogle Scholar
  23. 23.
    Browning MD, Bereau M, Dudek EM, Olsen RW. Protein kinase C and cAMP-dependent protein kinase phosphorylate the ß-subunit of the purified y-aminobutyric acid A receptor. Proc Natl Acad Sei USA 1990; 87:1315–1318.CrossRefGoogle Scholar
  24. 24.
    Roca DJ, Rozenberg I, Farrant M, Farb DH. Chronic agonist exposure induces down-regulation and allosteric uncoupling of the y-aminobutyric acid/ benzodiazepine receptor complex. Mol Pharmacol 1990; 37:37–43.PubMedGoogle Scholar
  25. 25.
    Hirouchi M, Ohkuma S, Kuriyama K. Muscimol-induced reduction of GABAA receptor arsubunit mRNA in primary cultured neuron. Mol Brain Res 1992; 15:327–331.PubMedCrossRefGoogle Scholar
  26. 26.
    Memo M, Bovolin P, Costa E, Grayson DR. Regulation of y-aminobutyric acidA receptor subunit expression by activation of N-methyl-D-aspartate-sensitive glutamate receptors. Mol Pharmacol 1991; 39:599–603.PubMedGoogle Scholar
  27. 27.
    Betz H, Becker CM. The mammalian glycine receptor: Biology and structure of a neuronal chloride channel protein. Neurochem Int 1988; 13:137–146.PubMedCrossRefGoogle Scholar
  28. 28.
    Langosch D, Thomas L, Betz H. Conceived quaternary structure of ligand-gated ion channels: The postsynaptic glycine receptor is a pentamer. Proc Natl Acad Sei USA 1988; 85:7394–7398.CrossRefGoogle Scholar
  29. 29.
    Grenningloh G, Rienitz A, Schmitt B, Methfessel C, Zensen M, Beyreuther K, Gundelfinger ED, Betz H. The strychnine-binding subunit of the glycine receptor shows homology with nicotinic acetylcholine receptors. Nature 1987; 328:215–220.PubMedCrossRefGoogle Scholar
  30. 30.
    Grenningloh G, Schmieden V, Schofield PR, Seeburg PH, Siddique T, Mohandas TK, Becker CM, Betz H. Alpha subunit variants of the human glycine receptor: Primary structures, functional expression and chromosomal localization of the corresponding genes. EMBO J 1990; 9:771–776.PubMedGoogle Scholar
  31. 31.
    Grenningloh G, Pribilla I, Prior P, Multhaup G, Beyreuther K, Taleb O, Betz H. Cloning and expression of the 58 kd ß subunit of the inhibitory glycine receptor. Neuron 1990; 4:963–970.PubMedCrossRefGoogle Scholar
  32. 32.
    Malosio ML, Grenningloh G, Kuhse J, Schmieden V, Schmitt B, Prior P, Betz H. Alternative splicing generates two variants of the subunit of the inhibitory glycine receptor. J Biol Chem 1991; 266:2048–2053.PubMedGoogle Scholar
  33. 33.
    Kuhse J, Kuryatov A, Maulet Y, Malosio ML, Schmieden V, Betz H. Alternative splicing generates two isoforms of the a subunit of the inhibitory glycine receptor. FEBS Lett 1991; 283:73–77.PubMedCrossRefGoogle Scholar
  34. 34.
    Schmiden V, Grenningloh G, Schofield PR, Betz H. Functional expression in Xenopus oocytes of the strychnine binding 48 kd subunit of the glycine receptor. EMBO J 1989; 8:695–700.Google Scholar
  35. 35.
    Akagi H, Hirai K, Hishinuma F. Cloning of a glycine receptor subtype expressed in rat brain and spinal cord during a specific period of neuronal development. FEBS Lett 1991; 281:160–166. PubMedCrossRefGoogle Scholar

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© Springer-Verlag New York, Inc. 1994

Authors and Affiliations

  • Kinya Kuriyama
  • Masaaki Hirouchi

There are no affiliations available

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