Structure and Pharmacology of Vertebrate GABAA Receptor Subtypes

International Review of Neurobiology - Tập 38 - Trang 95-138 - 1995
Paul J. Whiting1, Ruth M. McKernan1, Keith A. Wafford1
1Neuroscience Research Centre, Merck Sharp & Dohme, Harlow, Essex CM20 2QR, England

Tài liệu tham khảo

Akaike, 1991, Quinolones and fenbufen interact with GABAA receptor in dissociated hippocampal cells of rat, J. Neurophysiol., 66, 497, 10.1152/jn.1991.66.2.497 Amin, 1993, GABAA receptor needs two homologous domains of the β-subunit for activation by GABA but not by pentobarbital, Nature (London), 366, 565, 10.1038/366565a0 Amin, 1994, Homomeric ρl GABAA channels: Activation properties and domains, Recep. Channels, 2, 227 Angelman, 1965, “Puppet children”: A reporl on three cases, Dev. Med. Child. Neurol., 7, 681, 10.1111/j.1469-8749.1965.tb07844.x Angelotti, 1993, Assemhly of GABAA receptor subunits: αlβ2 and α1β2γ2S subunits produce unique ion channels with dissimilar ion channel properties, J. Neurosci, 13, 1429, 10.1523/JNEUROSCI.13-04-01429.1993 Angelotti, 1993, Assembly of GABAA receptor subunits: Analysis of transient single cell expression utilizing a fluorescent substrate/marker gene combination, J. Neurosci., 13, 1418, 10.1523/JNEUROSCI.13-04-01418.1993 Angelotti, 1993, Enhancement of γ-aminobutyric acid type A receptor currents by chronic activation of cAMPdependent protein kinase, Mol. Pharmacol., 44, 1202 Arena, 1993, Avermectins potentiate GABAsensitive current in Xenopus oocytes expressing cloned GABAA receptors, Biophys. J., 64, A325 Backus, 1993, Stoichiometry of a recombinant GABAA receptor deduced from mutation-induced rectification, NeuroReport, 5, 285, 10.1097/00001756-199312000-00026 Bateson, 1990, Sequence of the chicken GABAA receptor β3 subunit cDNA, Nucleic Acids Res., 18, 5557, 10.1093/nar/18.18.5557 Bateson, 1991, The chicken GABAA receptor α1 subunit: cDNA sequence and localization of the corresponding mRNA, Mol. Brain Res., 9, 333, 10.1016/0169-328X(91)90081-8 Bateson, 1991, γ-aminobutyric acid A receptor heterogeneity is increased by alternative splicing of a novel β-subunit gene transcript, J. Neurochem., 56, 1437, 10.1111/j.1471-4159.1991.tb11443.x Baude, 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 (Oxford), 51, 739, 10.1016/0306-4522(92)90513-2 Beattie, 1993, Developmental cues modulate GABAA receptor subunit mRNA expression in cultured cerebellar granule neurons, J. Neurosci., 13, 1784, 10.1523/JNEUROSCI.13-04-01784.1993 Belelli, 1994, Modulation of human (α1β1γ2I.) recombinant GABAA receptors by pregnanediols, Can. J. Physiol. Pharmacol., 72, P13318 Benke, 1990, Identification of the γ2 subunit protein in native GABA receptors in brain, Eur. J. Pharmacol., 189, 337, 10.1016/0922-4106(90)90127-J Benke, 1991, Identification and immunohistochemical mapping of GABAA receptor subtypes containing the δ subunit in rat brain, FEBS Lett., 283, 145, 10.1016/0014-5793(91)80573-L Benke, 1991, Immunochemical identification of the α1 and α3 subunits of the GABAA receptor in rat brain, J. Recept. Res., 11, 1, 10.3109/10799899109066418 Benke, 1991, Ubiquitous presence of GABAA receptors containing the α1 subunit in rat brain demonstrated by immunoprecipitation and immunohistochemistry, Mol. Neuropharmacol., 1, 103 Benke, 1991, GABAA receptors display association of γ2 subunit with α1 and β2/3 subunits, J. Biol. Chem., 266, 4478, 10.1016/S0021-9258(20)64347-2 Benke, 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, 2700, 10.1016/S0021-9258(18)47131-1 Bovolin, 1992, Expression patterns of γ-aminobutyric acid type A receptor subunit mRNAs in primary cultures of granule neurons and astrocytes from neonatal rat cerebella, Proc. Natl. Acad. Sci. U.S.A., 89, 9344, 10.1073/pnas.89.19.9344 Browning, 1990, Protein kinase C and CAMP dependent protein kinase phosphorylate the β-subunit of the purified GABAA receptor, Proc. Natl. Acad. Sd. U.S.A., 87, 1315, 10.1073/pnas.87.4.1315 Buckle, 1989, Chromosomal localization of GABAA receptor subunit genes: Relationship to human genetic disease, Neuron, 3, 647, 10.1016/0896-6273(89)90275-4 Concas, 1991, Neurochemical action of the general anesthetic propofol on the chloride ion channel coupled with GABAA receptors, Brain Res., 542, 225, 10.1016/0006-8993(91)91571-H Culiat, 1994, Phenotypic consequences of deletion of the γ3. α5. or β3 subunit of the type A γ-aminobutyric acid receptor of mice, Proc. Natl. Acad. Sci. U.S.A., 91, 2815, 10.1073/pnas.91.7.2815 Cutting, 1991, Cloning of the gamma-aminobutyric acid rhol cDNA A GABA receptor subunit highly expressed in retina, Proc. Natl. Acad. Sci. U.S.A., 88, 2673, 10.1073/pnas.88.7.2673 Cutting, 1992, Identification of a putative gamma-aminobutyric acid (GABA) receptor subunit ρ2 and colocalization of the genes encoding ρ2 (GABARR1) and ρl (GABARR1) to human chromosome 6q14-q2 and mouse chromosome-4, Genomics, 12, 801, 10.1016/0888-7543(92)90312-G Deitrich, 1989, Mechanism of action of ethanol: Initial central nervous system actions, Pharmacol. Rev., 41, 489 Draguhn, 1990, Function and molecular distinction between recombinant rat GABAA receptor subtypes in Zn2+, Neuron, 5, 781, 10.1016/0896-6273(90)90337-F Duggan, 1990, Biochemical evidence for the existence of γ-aminobutyrateA receptor isooligomers, J. Biol. Chem., 265, 3831, 10.1016/S0021-9258(19)39669-3 Duggan, 1991, Immunoaffinity purification of GABAA receptor a-subunit iso-oligomers. Demonstration of receptor populations containing α1α2, α1α3 and α2α3 subunit pairs, J. Biol. Chem., 266, 24778, 10.1016/S0021-9258(18)54297-6 Duggan, 1992, Quantitative immunoprecipitation studies with anti-γ-aminobutyric acidA receptor γ2 1–15 Cys antibodies, J. Neurochem., 58, 72, 10.1111/j.1471-4159.1992.tb09278.x Ebert, 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 Feigenspan, 1993, Pharmacology of GABA receptor Cl− channels in rat retinal bipolar cells, Nature (London), 361, 159, 10.1038/361159a0 Fernando, 1995, J. Neurochem., 64, 1305, 10.1046/j.1471-4159.1995.64031305.x Ffrench-Constant, 1991, Molecular cloning and transformation of cyclodiene resistance in Drosophila: An invertebrate γ-aminobutyric acid subtype A receptor locus, Proc. Natl. Acad. Sci. U.S.A., 88, 7209, 10.1073/pnas.88.16.7209 Ffrench-Constant, 1993, A point mutation in a Drosophila GABA receptor confers insecticide resistance, Nature (London), 363, 449, 10.1038/363449a0 Franks, 1994, Molecular and cellular mechanisms of general anaesthesia, Nature (London), 367, 607, 10.1038/367607a0 Fritschy, 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. U.S.A., 89, 6726, 10.1073/pnas.89.15.6726 Gao, 1993, Neuron-specific expression of GABAA receptor subtypes: Differential association of the α1 and α3 subunits with serotonergic and GABAergic neurons, Neuroscience (Oxford), 54, 881, 10.1016/0306-4522(93)90582-Z Gao, 1994, Selective allocation of GABAA receptors containing the α1 subunit to neurochemically distinct subpopulations of rat hippocampal interneuron, Eur. J. Neurosci., 6, 837, 10.1111/j.1460-9568.1994.tb00994.x Glencourse, 1993, Sequence and novel distribution of the chicken homologue of the mammalian γ-aminobutyric acidA receptor γ1 subunit, J. Neurochem., 61, 2294, 10.1111/j.1471-4159.1993.tb07473.x Glencourse, 1990, Sequence of the chicken GABAA receptor γ2 subunit cDNA, Nucleic Acids Res., 18, 7157, 10.1093/nar/18.23.7157 Gyenes, 1994, Phosphorylation factors control neurotransmitter and neuromodulator actions at the γ-aminobutyric acid type A receptor, Mol. Pharmacol., 46, 542 Hadingham, 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 Hadingham, 1993, The role of the beta subunit in determining the pharmacology of human GABAA receptors, Mol. Pharmacol., 44, 1211 Hadingham, K. L., Wafford, K. A., Thompson, S. A., Palmer, K. J., and Whiting, P. J. (in press). Expression and pharmacology of human γ-aminobutyric acidA receptors containing γ3 subunits Eur. J. Pharmacol. Hales, 1991, The actions of propofol on inhibitory amino acid receptors of bovine adrenomedullary chromfin cells and rodent central neurones, Br. J. Pharmacol., 104, 619, 10.1111/j.1476-5381.1991.tb12479.x Hales, 1992, Modulation of GABAA and glycine receptors by chlormethiozole, Eur. J. Pharmacol., 210, 239, 10.1016/0014-2999(92)90410-6 Hales, 1994, Few cell lines with GABAA mRNAs have funtional receptors, J. Neurosci., 14, 5429, 10.1523/JNEUROSCI.14-09-05429.1994 Hales, 1992, Immortalized hypotholamic GT1–7 neurons express functional GABAA receptors, Mol. Pharmacol., 42, 197 Haliwell, 1991, The effects of quinolones and NSAIDS upon GABA-evoked currents recorded from dorsal root ganglion neurones, J. Antimicrob. Chemother., 27, 209, 10.1093/jac/27.2.209 Hara, 1993, Propofol activates GABAA receptor-chloride ionophore complex in dissociated hippocampal neurons of the rat, Anesthesiology, 79, 781, 10.1097/00000542-199310000-00021 Harvey, 1993, Molecular cloning reveals the existence of a fourth γ subunit of the vertebrate brain GABAA receptor, FEBS htt., 331, 211, 10.1016/0014-5793(93)80339-V Harvey, 1994, Alternative splicing of a 51 nucleotide exon that encodes a putative protein kinase C phosphorylation site generates 2 forms of the chicken γ-aminobutyric acidA receptor β2 subunit, J. Neurochem., 62, 10, 10.1046/j.1471-4159.1994.62010010.x Herb, 1992, The third γ subunit of the γ-aminobutyric acid type A receptor family, Proc. Natl. Acad. Sci. U.S.A., 89, 1433, 10.1073/pnas.89.4.1433 Heuschneider, 1989, cAMP and forskolin decrease gamma-aminobutyric acid gated chloride flux in rat brain synaptoneurosomes, Proc. Natl. Acad. Sci. U.S.A., 86, 2938, 10.1073/pnas.86.8.2938 Hicks, 1994, Further evidence for clustering of human GABAA receptor subunit genes: Localization of the & subunit gene (GABRAG) to distal chromosome 5q by linkage analysis, Genomics, 20, 285, 10.1006/geno.1994.1167 Holland, 1990, Physiological modulation of the picrotoxin receptor by γ-butyrolactones and γ-thiobutyrolactones in cultured hippocampal neurons, J. Neurosci., 10, 1719, 10.1523/JNEUROSCI.10-06-01719.1990 Horne, 1992, The pharmacology of recombinant GABAA receptors containing α1, β1, γ2L subunits stably transfected into mouse L-cells, Br. J. Pharmacol., 107, 732, 10.1111/j.1476-5381.1992.tb14515.x Horne, 1993, The influence of the γ2L subunit on the modulation of responses to GABAA receptor activation, Br. J. Pharmacol., 108, 711, 10.1111/j.1476-5381.1993.tb12866.x Huganir, 1990, Regulation of neurotransmitter receptor desensitization by protein phosphorylation, Neuron, 5, 555, 10.1016/0896-6273(90)90211-W Im, 1992, Selective potentiation of GABAA mediated CI− current by lanthanum ion in subtypes of cloned GABAA receptors, Neurosci. Lett., 144, 165, 10.1016/0304-3940(92)90741-O Im, 1993, Potentiation of γ-aminobutyric acid-induced chloride currents by various benzodiapine site agonists with the αlγ2, β2γ2, and α1β2γ2 subtypes of cloned γ-aminobutyric acid type A receptors, Mol. Pharmacol., 44, 866 Im, 1993, Substituted pyrazinones, a new class of allosteric modulators for γ-aminobutyric acidA receptors, Mol. Pharmacol., 44, 468 Jackson, 1982, Single channel currents activated by γ-aminobutyric acid, muscimol and (-)pentobarbital in cultured mice spinal neurons, J. Neurosti., 2, 889, 10.1523/JNEUROSCI.02-07-00889.1982 Johnston, 1986, Multiplicity of GABA receptors, 5, 57 Jones, 1992, Enhancement of γ-aminobutyric acid Cl− currents in cultured rat hippocampal neurones by three volatile anaesthetics, J. Physiol. (London), 449, 279, 10.1113/jphysiol.1992.sp019086 Kang, 1994, Isolation and characterization of the promoter of the human GABAA receptor α1 subunit gene, J. Neurochem., 62, 1643, 10.1046/j.1471-4159.1994.62041643.x Kato, 1990, Novel GABAA receptor α subunit is expressed only in cerebellar granule cells, Mol. Biol., 214, 619, 10.1016/0022-2836(90)90276-R Kellenberger, 1992, Function of the α1β2γ2S γ-aminobutyric acid type A receptor is modulated by protein kinase C via multiple sites, J. Biol. Chem., 267, 25660, 10.1016/S0021-9258(18)35656-4 Keir, 1991, The cDNA sequence and chromosomal location of the murine GABAA α1 receptor gene, Genomics, 9, 390, 10.1016/0888-7543(91)90272-G Kern, 1994, Polyclonal antibodies directed against an epitope specific for the α-4-subunit of GABAA receptors identify a 67-kDa protein in rat brain membranes, J. Neurochem., 62, 764, 10.1046/j.1471-4159.1994.62020764.x Khan, 1994, The subunit composition of a GABAA/benzodiazepine receptor from rat cerebellum, J. Neurochem., 63, 371, 10.1046/j.1471-4159.1994.63010371.x Khan, 1994, The short and long form γ2 subunits of the GABAA/benzodiazepine receptors, J. Neurochem., 63, 1466, 10.1046/j.1471-4159.1994.63041466.x Khrestchatisky, 1989, A novel α subunit in rat brain GABAA receptors, Neuron, 3, 745, 10.1016/0896-6273(89)90243-2 Khrestchatisky, 1991, Sequence and regional distribution of the mRNA encoding the α2 polypeptide of rat γ-aminobutyric acidA receptors, J. Neurochem., 56, 1717, 10.1111/j.1471-4159.1991.tb02072.x Kirkness, 1991, Isolation, characterization and localization of human genomic DNA encoding the β1 subunit of the GABAA receptor (GABRB1), Genomics, 10, 985, 10.1016/0888-7543(91)90189-L Kirkness, 1993, A strong promoter element is located between alternative exons of a gene encoding the human GABAR β3 subunit (GABRB3), J. Biol. Chem., 268, 4420, 10.1016/S0021-9258(18)53626-7 Knoflach, 1991, The γ3-subunit of the GABAA receptor confers sensitivity to GABAA receptor ligands, FEBS Lett., 293, 191, 10.1016/0014-5793(91)81184-A Knoflach, 1992, Pharmacological and electrophysiological properties of recombinant GBAA receptors comprising the α3, β1 and γ2 subunits, Eur. J. Neurosci., 4, 1, 10.1111/j.1460-9568.1992.tb00103.x Knoll, 1993, Ordering of reference markers and assignment of the GABAA receptor α5 subunit gene within the Angelman and Prader-Willi chromosomal regions, Hum. Mol. Genet., 2, 183, 10.1093/hmg/2.2.183 Kofuji, 1991, Generation of two forms of the γ-aminobutyric acidA receptor γ2-subunit in mice by alternative splicing, J. Neurochem., 56, 713, 10.1111/j.1471-4159.1991.tb08209.x Korpi, 1993, Regional GABA sensitivity of [35S]TBPS binding depends on GABAA receptor α subunit, Mol. Pharmacol., 44, 87 Korpi, 1994, Small N-terminal deletion by splicing in cerebellar α6 subunit abolishes GABAA receptor function, J. Neurochem., 63, 1167, 10.1046/j.1471-4159.1994.63031167.x Krishek, 1994, Regulation of GABAA receptor function by protein kinase C phosphorylation, Neuron, 12, 1081, 10.1016/0896-6273(94)90316-6 Krusek, 1994, Effect of ivermectin on γ-aminobutyric acid-induced chloride currents in mouse hippocampal embryonic neurones, Eur. J. Pharmacol., 259, 121, 10.1016/0014-2999(94)90500-2 Kusama, 1993, Pharmacology of GABA ρl and GABA α1/β1 receptors expressed in Xenopus oocytes and COS cells, Br. J. Pharmacol., 109, 200, 10.1111/j.1476-5381.1993.tb13554.x Kusama, 1993, GABA ρ2 receptor pharmacological profile: GABA recognition site similarities to ρ1, Eur. J. Pharmacol., 245, 83, 10.1016/0922-4106(93)90174-8 Lan, 1991, Differential responses of expressed recombinant human γ-aminobutyric acidA receptors to neurosteroids, J. Neurochem., 57, 1818, 10.1111/j.1471-4159.1991.tb06388.x Laurie, 1992, The distribution of 13 GABAA receptor subunit mRNAs in the rat brain II. Olfactory bulb and cerebellum, J. Neurosci., 12, 1063, 10.1523/JNEUROSCI.12-03-01063.1992 Legendre, 1991, Noncompetitive inhibition of γ-aminobutyric acidA channels by Zn, Mol. Pharmacol., 39, 267 Leidenheimer, 1992, Activation of protein kinase C selectively inhibits the γ-aminobutyric acidA receptor: Role of desensitization, Mol. Pharmacol., 41, 1116 Levitan, 1988, Structural and functional basis for GABAA receptor heterogeneity, Nature (London), 335, 76, 10.1038/335076a0 Lin, 1992, General anesthetics potentiate γ-aminobutyric acid actions on γ-aminobutyric acid, receptors expressed by Xenopus oocytes: Lack of involvement of intracellular calcium, J. Pharmacol. Exp. Ther., 263, 569 Lin, 1993, Molecular determinants of general anesthetic action: Role of GABA, receptor structure, J. Neurochem., 60, 1548, 10.1111/j.1471-4159.1993.tb03320.x Lolait, 1989, Pharmacological characterization and region specific expression in brain of the β2 and β3 subunits of the rat GABAA receptor, FEBS Lett., 1, 17, 10.1016/0014-5793(89)81605-9 Lüddens, 1990, Cerebellar GABAA receptor selective for a behavioral alcohol antagonist, Nature (London), 346, 648, 10.1038/346648a0 Lüddens, 1991, More than one α variant may exist in a GABAA/benzodiazepine receptor complex, J. Recept. Res., 11, 535, 10.3109/10799899109066426 Lüddens, 1994, Impact of β and γ variants on ligand binding properties of γ-aminobutyric acid type A receptors, Mol. Pharmacol., 45, 810 Lukasiewicz, 1994, A novel GABA receptor on bipolar cell terminals in the tiger salamandar retina, J. Neurosci., 14, 1202, 10.1523/JNEUROSCI.14-03-01202.1994 Ma, 1994, Terbium modulation of single γ-aminohutyric acid-activated chloride channels in rat dorsal root ganglion neurons, J. Neurosci., 14, 3835, 10.1523/JNEUROSCI.14-06-03835.1994 Macdonald, 1994, GABAA receptor channels, Annu. Rev. Neurosci., 17, 569, 10.1146/annurev.ne.17.030194.003033 Macdonald, 1989, Kinetic properties of the GABAA receptor main conductance state of mouse spinal cord neurons in culture, J. Physiol. (London), 417, 483, 10.1113/jphysiol.1989.sp017814 Machu, 1993, Ca2+/Calmodulin dependent protein kinase II and protein kinase C phosphorylate a synthetic peptide corresponding to a sequence that is specific for the γ2L subunit of the GABAA-receptor, J. Neurochem., 61, 375, 10.1111/j.1471-4159.1993.tb03582.x McKernan, 1991, GABAA receptor subtypes immunopurified from rat brain with α subunit specific antibodies have unique pharmacological properties, Neuron, 7, 667, 10.1016/0896-6273(91)90379-E Majewska, 1986, Steroid hormone metabolites are barbiturate like modulators of the GABA receptor, Science, 232, 1004, 10.1126/science.2422758 Majewska, 1988, Neurosteroid pregnenelone sulfate antagonizes electrophysiological responses to GABA in neurons, Neurosci. Lett., 90, 279, 10.1016/0304-3940(88)90202-9 Majewska, 1990, The neurosteroid dehydroepiandrosterone sulfate is an allosteric antagonist of the GABAA receptor, Brain Res., 526, 143, 10.1016/0006-8993(90)90261-9 Malherbe, 1990, Functional expression and sites of gene transcription of a novel α subunit of the GABAA receptor in rat brain, FEBS Lett., 260, 261, 10.1016/0014-5793(90)80118-3 Malminiemi, 1989, Diazepam-insensitive [3H]Ro 15–4513 binding to intact cultured cerebellar granule cells, Eur. J. Pharmacol., 169, 53, 10.1016/0014-2999(89)90816-9 Marksiaer, 1993, GABAA receptors: Drug binding profile and distribution of receptors containing the α2 subunit in situ, J. Recept. Res., 13, 467, 10.3109/10799899309073673 Mathews, 1994, Developmental alteration in GABAA receptor structure and physiological properties in cultured cerebellar granule cells, Neuron, 13, 149, 10.1016/0896-6273(94)90465-0 Mertens, 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, 10.1016/S0021-9258(18)53413-X Mihic, 1994, Anaesthetic concentrations of alcohols potentiate GABAA receptor mediated currents: Lack of subunit selectivity, Eur. J. Pharmacol., 268, 209, 10.1016/0922-4106(94)90190-2 Mihic, 1994, A single amino acid of the human GABAA receptor γ2 subunit determines benzodiazepine efficacy, J. Biol. Chem., 269, 32768, 10.1016/S0021-9258(20)30057-0 Moody, 1989, Chlormethiozole: Neurochemical actions at the γ-aminobutyric acid receptor complex, Eur. J. Pharmacol., 164, 153, 10.1016/0014-2999(89)90242-2 Moss, 1992, Science, 257, 661, 10.1126/science.1323140 Moss, 1992, Identification of the cAMP dependent protein kinase and protein kinase phosphorylation sites within the major intracellular domains of the β1, γ2S and γ2L subunits of the γ-aminobutyric acid type A receptor, J. Biol. Chem., 267, 14470, 10.1016/S0021-9258(19)49736-6 Motejlek, 1994, BSF1, a novel brain specific DNA-binding protein recognizing a tandemly repeated purine DNA element in the GABAA receptor δ subunit gene, J. Biol. Chem., 269, 15265, 10.1016/S0021-9258(17)36601-2 Nakatsu, 1993, A cluster of 3 GABA receptor subunit genes is deleted in a neurological mutant of the mouse p-locus, Nature (London), 364, 448, 10.1038/364448a0 Nayeem, 1994, Quaternary structure of the native GABAA receptor determined by electron microscopic image analysis, J. Neurochem., 62, 815, 10.1046/j.1471-4159.1994.62020815.x Newland, 1992, On the mechanism of action of picrotoxin on GABA receptor channels in dissociated sympathetic neurones of the rat, J. Physiol. (London), 447, 191, 10.1113/jphysiol.1992.sp018998 Noble, 1993, Identification of the GABAA receptor α3 subunit in the IMR-32 neuroblastoma cell line, J. Neurochmn., 61, 752, 10.1111/j.1471-4159.1993.tb02182.x Parfitt, 1990, Potentiation of gamma-aminobutyric acid-mediated inhibition by isoproterenol in the cerebellar cortex: Receptor specificity, Neuropharmacology, 29, 909, 10.1016/0028-3908(90)90141-D Peoples, 1994, Trichloroethanol potentiation of γ-aminobutyric acid-activated chloride current in mouse hippocampal neurones, Br. J. Pharmacol., 113, 555, 10.1111/j.1476-5381.1994.tb17025.x Persohn, 1992, Comparative molecular neuroanatomy of cloned GABAA receptor subunits in the rat CNS, J. Comp. Neurol., 326, 193, 10.1002/cne.903260204 Polenzani, 1991, Expression of mammalian γ-aminobutyric acid receptors with distinct pharmacology in Xenopus oocytes, Proc. Natl. Acad. Sci. U.S.A., 88, 4318, 10.1073/pnas.88.10.4318 Pollard, 1993, Further evidence for the existence of a subunit heterogeneity within discrete γ-aminobutyric acidA receptor subpopulations, J. Biol. Chem., 268, 3753, 10.1016/S0021-9258(18)53758-3 Pong, 1982, Avermectin Bla modulation of GABAA receptors in rat brain membranes, J. Neurochem., 38, 375, 10.1111/j.1471-4159.1982.tb08639.x Porter, 1990, Cyclic AMP dependent protein kinase decreases GABAA receptor current in mouse spinal neurons, Neuron, 5, 789, 10.1016/0896-6273(90)90338-G Pribilla, 1992, The atypical M2 segment of the β subunit confers picrotoxinin resistance to inhibitory glycine receptor channels, EMBO J., 11, 4305, 10.1002/j.1460-2075.1992.tb05529.x Pritchett, 1989, Type I and type II GABAA benzodiazepine receptor produced in transfected cells, Science, 245, 1389, 10.1126/science.2551039 Pritchett, 1989, Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology, Nature (London), 338, 582, 10.1038/338582a0 Pritchett, 1990, Gamma aminobutyric acidA receptor α5 subunit creates novels type II benzodiazepine receptor pharmacology, J. Neurochem., 54, 1802, 10.1111/j.1471-4159.1990.tb01237.x Pritchett, 1991, γ-aminobutyric acid type A receptor point mutation increases the affinity of compounds for the benzodiazepine site, Proc. Natl. Acad. Sci. U.S.A., 88, 1421, 10.1073/pnas.88.4.1421 Proctor, 1992, Brain region-dependent sensitivity of GABAA receptor-mediated responses to modulation by ethanol, Alcohol. Clin. Exp. Res., 16, 480, 10.1111/j.1530-0277.1992.tb01405.x Puia, 1990, Neurosteroids act on recombinant GABAA receptors, Neuron, 4, 759, 10.1016/0896-6273(90)90202-Q Puia, 1991, Influence of recombinant γ-aminobutyric acidA receptor subunit compositions on the action of allosteric modulator of γ-aminobutyric acidgated chloride currents, Mol. Pharmacol., 39, 691 Puia, 1992, 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. U.S.A., 89, 3620, 10.1073/pnas.89.8.3620 Qian, 1993, Novel GABA responses from roddriven retinal horizontal cells, Nature (London), 361, 162, 10.1038/361162a0 Quirk, 1994, Model of subunit composition of γ-aminobutyric acid A receptor subtypes expressed in rat cerebellum with respect to their α and γ/δ subunits, J. Biol. Chem., 269, 16020, 10.1016/S0021-9258(17)33967-4 Quirk, 1994, γ-aminobutyric acid type A receptors in rat brain can contain both γ2 and γ3 subunits, but γ1 does not exist in combination with another γ subunit, Mol. Pharmacol., 45, 1061 Sakmann, 1983, Patch-clamp measurements of elementary chloride currents activated by the putative inhibitory transmitters GABA and glycine in mammalian spinal neurons, J. Neural Transm. Suppl., 18, 83 Sapp, 1992, Regional variation in steroid anaesthetic modulation of [3H]TBPS binding to γ-aminobutyric acid receptors in rat brain, J. Pharmacol. Exp. Ther., 262, 801 Saxena, 1994, Assembly of GABA-A receptor subunits: role of the β subunit, J. Neurosci., 14, 7077, 10.1523/JNEUROSCI.14-11-07077.1994 Schofield, 1987, Sequence and functional expression of the GABAA receptor shows a ligand gated ion channel family, Nature (London), 328, 221, 10.1038/328221a0 Schofield, 1989, Sequence and expression of human GABA, receptor α1 and β1 subunits, FEBS Lett., 244, 361, 10.1016/0014-5793(89)80563-0 Seeburg, 1990, The GABAA receptor family: Molecular and functional diversity, Cold Spring Harbor Symp. Quant. Biol., 55, 29, 10.1101/SQB.1990.055.01.006 Sessler, 1989, Noradrenergic potentiation of cerebellar purkinjee cell responses to GABA: Evidence for mediation through the β-adrenoceptor-coupled cyclic AMP system, Brain Res., 499, 27, 10.1016/0006-8993(89)91132-3 Shimada, 1992, γ-aminobutyric acid A or C receptor? γ-aminobutyric acid ρ1 receptor RNA induces bicuculline, barbiturate and benzodiazepine insensitive γ-aminobutyric acid responses in Xenopus oocytes, Mol. Pharmacol, 41, 683 Shingai, 1991, Effects of subunit types of the cloned GABAA receptor on the response to a neurosteroid, Eur. J. Pharmacol., 206, 77, 10.1016/0922-4106(91)90149-C Shivers, 1989, Two novel GABAA receptor subunits exist in distinct neuronal populations, Neuron, 3, 327, 10.1016/0896-6273(89)90257-2 Sieghart, 1983, Irreversible binding of [3H] flunitrazepam to different proteins in various brain regions, J. Neurochem., 41, 47, 10.1111/j.1471-4159.1983.tb11812.x Sieghart, 1987, Photoaffinity labelling of benzodiazepine receptor proteins with partial inverse agonist [3H] Ro 15–4513: A biochemical and autoradiographic study, J. Neurochem., 48, 46, 10.1111/j.1471-4159.1987.tb13125.x Sieghart, 1993, Evidence for the existence of differential O-glycosylated α5-subunits of the γ-aminobutyric acidA receptor in the rat brain, J. Neurochem., 60, 93, 10.1111/j.1471-4159.1993.tb05826.x Sigel, 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, 10.1016/S0021-9258(17)39860-5 Sigel, 1988, Activation of protein kinase C differentially modulates neuronal Na+, Ca2+, and γ-aminobutyrate type A channels, Proc. Natl. Acad. Sci. U.S.A., 85, 6192, 10.1073/pnas.85.16.6192 Sigel, 1990, The effect of subunit composition of rat brain GABAA receptors on channel funciton, Neuron, 5, 703, 10.1016/0896-6273(90)90224-4 Sigel, 1992, Point mutations affecting antagonist and agonist dependent gating of GABAA receptor channels, EMBO J., 11, 2017, 10.1002/j.1460-2075.1992.tb05258.x Sinnett, 1993, High resolution mapping of the γ-aminobutyric acid receptor β3 and α5 gene cluster on chromosome 15q11–15q13, and localization of breakpoints in two Angelman Syndrome patients, Am. J. Hum. Genet., 52, 1216 Smart, 1992, A novel modulatory binding site for zinc on the GABAA receptor complex in cultured rat neurones, J. Physiol. (London), 447, 587, 10.1113/jphysiol.1992.sp019020 Smart, 1986, Studies on the mechanism of action of picrotoxinin and other convulsants at the crustacean muscle GABAA receptor, Proc. R. Soc. London B, 277, 191, 10.1098/rspb.1986.0019 Smart, 1990, Studieson the mechanism of action of picrotoxinin and other convulsants at the crustacean muscle GABAA receptor, Br. J. Pharmacol., 99, 643, 10.1111/j.1476-5381.1990.tb12984.x Smart, 1991, GABAA receptors are differentially sensitive to zinc-dependence on subunit composition, Br. J. Pharmacol., 103, 1837, 10.1111/j.1476-5381.1991.tb12337.x Smith, 1994, Identification of a [3H]muscimol photoaffinity substrate in the bovine γ-aminobutyric acidA recptor α subunit, J. Biol. Chem., 269, 20380, 10.1016/S0021-9258(17)32003-3 Sommer, 1990, The murine GABAA receptor β-subunit gene: Structure and assignment to human chromosome 1, DNA Cell Biol., 9, 561, 10.1089/dna.1990.9.561 Somogyi, 1989, Subcellular localization of benzodiazepine/GABAA receptors in the cerebellum of rat, cat and monkey using monoclonal antibodies, J. Neurosci., 9, 2197, 10.1523/JNEUROSCI.09-06-02197.1989 Squires, 1993, Indomethacin/Ibuprofen-like anti-inflammatory agents selectively potentiate the γ-aminobutyric acid-antagonistic effects of several norfloxacin-like quinolone antibacterial agents on [35S] t-butylbicyclophosphorothionate binding, Mol. Pharmacol., 43, 795 Squires, 1979, Some properties of brain specific benzodiazepine receptor: New evidence for multiple receptors, Pharmacol. Biochem. Behav., 10, 825, 10.1016/0091-3057(79)90341-1 Stelzer, 1988, GABAA receptor function in hippocampal cells is maintained by phosphorylation factors, Science, 241, 339, 10.1126/science.2455347 Stephenson, 1988, Understanding the GABAA receptor: A chemically gated ion channel, Biochem. J., 249, 21, 10.1042/bj2490021 Stephenson, 1990, The γ2 subunit is an integral component of the γ-aminobutyric acidA receptor but the α1 polypeptide is the principle site of the agonist benzodiazepine photoaffinity labelling reaction, J. Biol. Chem., 265, 21160, 10.1016/S0021-9258(17)45340-3 Tehrani, 1989, cAMP increases the rate of GABAA receptor desensitization in chick cortical neurons, Synapse, 4, 126, 10.1002/syn.890040206 Thompson, 1994, GABAA receptor subtypes expressed in cerebellar granule cells: A developmental study, J. Neurochem., 62, 2037, 10.1046/j.1471-4159.1994.62052037.x Thompson, 1995, Alpha subunits influence the action of pentobarbital on recombinant GABAA receptors, Br. J. Pharmacol. Ticku, 1990, γ-aminobutyric acid, receptor desensitization in mice spinal cord cultured neurons: Lack of involvement of protein kinases A and C, Mol. Pharmacol., 38, 719 Tokutomi, 1994, Effects of lindane (γ-HCH) and related convulsants on GABAA receptor-operated chloride channels in frog dorsal root ganglion neurons, Brain Res., 643, 66, 10.1016/0006-8993(94)90009-4 Togel, 1994, γ-aminobutyric acidA receptors displaying association of γ3-subunits with β2/3 and different α-subunits exhibit unique pharmacological properties, J. Biol. Chem., 269, 12993, 10.1016/S0021-9258(18)99974-6 Turner, 1989, Steroid anasthetics and naturally occurring analogs modulate the γ-aminobutyric acid receptor complex at a site distinct from barbiturates, J. Pharmacol. Exp. Ther., 248, 960 Twyman, 1992, Neurosteroid regulation of GABAA receptor single channel kinetic properties, J. Physiol. (London), 456, 215, 10.1113/jphysiol.1992.sp019334 Tyndale, 1994, Distinctive patterns of GABAA receptor subunit mRNAs in 13 cell lines, J. Neurosci., 14, 5417, 10.1523/JNEUROSCI.14-09-05417.1994 Unwin, 1989, The structure of ion channels in the membranes of excitable cells, Neuron, 3, 565, 10.1016/0896-6273(89)90235-3 Verdoorn, 1990, Functional properties of recombinant rat GABAA receptors depend upon subunit composition, Neuron, 4, 919, 10.1016/0896-6273(90)90145-6 Wafford, 1992, Ethanol potentiation of GABAA receptors requires phosphorylation of the alternatively spliced variant of the γ2 subunit, FEBS Lett., 313, 113, 10.1016/0014-5793(92)81424-K Wafford, 1991, Ethanol sensitivity of the GABAA receptor expressed in Xenopus oocytes requires eight amino acids contained in the γ2L subunit, Neuron, 7, 27, 10.1016/0896-6273(91)90071-7 Wafford, 1992, Differences in affinity and efficacy of benzodiazepine receptor ligands on recombinant GABAA receptor subtypes, Mol. Pharmacol., 43, 240 Wafford, 1993, Functional comparison of the role of γ-subunits in recombinant human γ-aminobutyric acid A/benzodiazepine receptors, Mol. Pharmacol, 44, 437 Wafford, 1994, A novel allosteric modulatory site on the GABAA receptor p subunit, Neuron, 12, 775, 10.1016/0896-6273(94)90330-1 Wagstaff, 1991, The GABAA receptor β3 subunit gene: Characterization of a human cDNAfrom chromosome 15q11q13 and mapping to a region of conserved synteny on mouse chromosome 7, Genomics, 11, 1071, 10.1016/0888-7543(91)90034-C Wang, 1992, The α1, α2, and α3 subunits of the GABAA receptor: Comparison in seizure prone and resistant mice and during development, J. Mol. Neurosci., 3, 177, 10.1007/BF03380136 Whiting, 1990, Another mechanism for creating diversity in γ-aminobutyrate type A receptors: RNA splicing directs expression two forms of the γ2 subunit, one of which contains a protein kinase C phosphorylation site, Proc. Natl. Acad. Sci. U.S.A., 87, 9966, 10.1073/pnas.87.24.9966 Wieland, 1992, A single histidine in GABAA receptors is essential for benzodiazepine agonist binding, J. Biol. Chem., 267, 227, 10.1016/S0021-9258(18)45961-3 Wilcox, 1992, Human chromosomal localisation of genes encoding the γ1 and γ2 subunits of the GABAA receptor indicates members of the gene family are often clustered in the genome, Proc. Natl. Acad. Sci. U.S.A., 89, 5857, 10.1073/pnas.89.13.5857 Williams, 1989, Incidence of 15q deletion in the Angelman syndrome: A survey of twelve affected people, Am. J. Med. Genet., 32, 339, 10.1002/ajmg.1320320313 Wilson-Shaw, 1991, A. novel γ subunit of the GABAA receptor identified using the polymerase chain reaction, FEBS Lett., 284, 211, 10.1016/0014-5793(91)80687-X Wingrove, 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 subunits, Proc. Natl. Acad. Sci. U.S.A., 91, 4569, 10.1073/pnas.91.10.4569 Wingrove, 1991, Cloning and expression of a cDNA encoding the human GABAA receptor α5 subunit, Biochem. Soc. Trans., 20, 17S Wisden, 1991, Cloning, pharmacological characteristics and expression pattern of rat GABAA receptor α4 subunit, FEBS Lett., 289, 227, 10.1016/0014-5793(91)81076-K Wisden, 1992, The distribution of 13 GABAA receptor subunit mRNAs in rat brain I. Telencephalon, diencephalon, mesencephalon, J. Neurosci., 12, 1040, 10.1523/JNEUROSCI.12-03-01040.1992 Woodward, 1992, Effects of hexachlorocyclohexanes on γ-aminobutyric acid receptors expressed in Xenopus oocytes by poly(A)+ RNA from mammalian brain and retina, Mol. Pharmacol, 41, 1107 Woodward, 1993, Characterization of bicuculline/baclofen-insensitive (plike) γ-aminobutyric acid receptors expressed in Xenopus oocytes. II. Pharmacology of γ-aminobutyric acidA and γ-aminobutyric acids receptor agonists and antagonists, Mol. Pharmacol., 43, 609 Yang, 1994, Identification of the GABAA receptor subtype mRNA in human pancreatic tissue, FEBS Lett., 346, 257, 10.1016/0014-5793(94)00485-4 Yeh, J. Z., Quandt, F. N., Tanguy, J., Nakahiro, M., Narahashi, T., and Brunner, E. A. (1991). General anesthetic action on γ-aminobutlyic acid-activated channels. In “Molecular and Cellular Mechanisms of Alcohol and Anesthetics” (E. Rubin, K. W. Miller and S. H. Roth, eds.) Ann. N. Y. Acad. Sci. 625, 155–173. Ymer, 1989, GABAA receptor beta subunit heterogeneity: Functional expression of cloned cDNAs, EMBO J., 8, 1665, 10.1002/j.1460-2075.1989.tb03557.x Ymer, 1990, Structural and functional characterization of the γ1 subunit of GABA benzodiazepine receptors, EMBO J, 9, 3261, 10.1002/j.1460-2075.1990.tb07525.x Zhang, 1994, A unique amino acid of the Drosophila GABA receptor with influence on drug sensitivity by two mechanisms, J. Physiol. (London), 479, 65, 10.1113/jphysiol.1994.sp020278