Abstract
The amino acid γ-aminobutyric-acid (GABA) prevails in the CNS as an inhibitory neurotrans-mitter that mediates most of its effects through fast GABA-gated Cl−-channels (GABAAR). Molecular biology uncovered the complex subunit architecture of this receptor channel, in which a pentameric assembly derived from five of at least 17 mammalian subunits, grouped in the six classes α, β, γ, δ, ε, and ρ, permits a vast number of putative receptor isoforms. The subunit composition of a particular receptor determines the specific effects of allosterical modulators of the GABAARs like benzodiazepines (BZs), barbiturates, steroids, some convulsants, polyvalent cations, and ethanol. To understand the physiology and diversity of GABAARs, the native isoforms have to be identified by their localization in the brain and by their pharmacology. In heterologous expression systems, channels require the presence of α, β, and γ subunits in order to mimic the full repertoire of native receptor responses to drugs, with the BZ pharmacology being determined by the particular α and γ subunit variants. Little is known about the functional properties of the β, δ, and ε subunit classes and only a few receptor subtype-specific substances like loreclezole and furosemide are known that enable the identification of defined receptor subtypes. We will summarize the pharmacology of putative receptor isoforms and emphasize the characteristics of functional channels. Knowledge of the complex pharmacology of GABAARs might eventually enable site-directed drug design to further our understanding of GABA-related disorders and of the complex interaction of excitatory and inhibitory mechanisms in neuronal processing.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Akaike N., Tokutomi N. and Ikemoto Y. (1990) Augmentation of GABA-induced current in frog sensory neurons by pentobarbital.Am. J. Physiol. 258, C452–460.
Alkon, D. L., Sanchez Andres J. V., Ito, E., Oka, K., Yoshioka T. and Collin, C. (1992) Long-term transformation of an inhibitory into an excitatory GABAergic synaptic response.Proc. Natl. Acad. Sci. USA 89, 11,862–11,866.
Allan A. M. and Harris R. A. (1986) γ-aminobutyric acid and alcohol actions: neurochemical studies of long sleep and short sleep mice.Life Sci. 39, 2005–2015.
Amin J. and Weiss D. S. (1993) GABAA receptor needs two homologous domains of the β-subunit for activation by GABA but not by pentobarbital [see comments].Nature 366, 565–569.
Angelotti T. P. and Macdonald R. L. (1993) Assembly of GABAA receptor subunits: α1 β1 and α1 β1 γ2S subunits produce unique ion channels with dissimilar single-channel properties.J. Neurosci. 13, 1429–1440.
Angelotti T. P., Tan F., Chahine K. G. and Macdonald R. L. (1992) Molecular and electrophysiological characterization of a allelic variant of the rat α 6 GABAA receptor subunit.Brain Res. Mol. Brain Res. 16, 173–178.
Angelotti T. P., Uhler M. D. and Macdonald R. L. (1993) Assembly of GABAA receptor subunits: analysis of transient single-cell expression utilizing a fluorescent substrate/marker gene technique.J. Neurosci. 13, 1418–1428.
Angelotti T. P., Uhler M. D. and Macdonald R. L. (1993) Enhancement of recombinant γ-aminobutyric acid type A receptor currents by chronic activation of cAMP-dependent protein kinase.Mol. Pharmacol. 44, 1202–1210.
Arbilla S., Allen, J., Wick, A. and Langer S. Z. (1986) High affinity [3H]zolpidem binding in the rat brain: an imidazopyridine with agonist properties at central benzodiazepine receptors.Eur. J. Pharmacol 130, 257–263.
Asano T. and Ogasawara N. (1982) Stimulation of GABA receptor binding by barbiturates.Eur. J. Pharmacol. 77, 355–357.
Asano, T., Sakakibara, J. and Ogasawara, N. (1983) Molecular sizes of photolabeled GABA and benzodiazepine receptor proteins are identical.FEBS Lett. 151, 277–280.
Ashton D., Fransen J., Heeres J., Clincke G. H. and Janssen P. A. (1992) In vivo studies on the mechanism of action of the broad spectrum anticonvulsant loreclezole.Epilepsy Res. 11, 27–36.
Avoli, M. (1992) Synaptic activation of GABAA receptors causes a depolarizing potential under physiological conditions in rat hippocampla pyramidal cells.Eur. J. Neurosci. 4, 16–26.
Avoli, M. and Perreault, P. (1987) A GABAergic depolarizing potential in the hippocampus disclosed by the convulsant 4-aminopyridine.Brain Res. 400, 191–195.
Backus K. H., Arigoni M., Drescher U., Scheurer L., Malherbe P., Mohler H. and Benson J. A. (1993) Stoichiometry of a recombinant GABAA receptor deduced from mutation-induced rectification.Neuroreport 5, 285–288.
Ballanyi K. and Grafe P. (1985) An intracellular analysis of γ-aminobutyric-acid-associated ion movements in rat sympathetic neurones.J. Physiol. Lond. 365, 41–58.
Barker, J. L., Harrison, N. L., Lange, G. D. and Owen, D. G. (1987) Potentiation of γ-aminobutyric-acid-activated chloride conductance by a steroid anaesthetic in cultured rat spinal neurones.J. Physiol. Lond. 386, 485–501.
Barker, J. L., Owen D. G. and Segal, M. (1984) GABA actions on the excitability of cultured CNS neurons.Neurosci. Lett. 47, 313–318.
Basile A. S., Bolger G. T., Lueddens H. W. and Skolnick P. (1989) Electrophysiological actions of Ro5-4864 on cerebellar Purkinje neurons: evidence for “peripheral” benzodiazepine receptor-mediated depression.J. Pharmacol. Exp. Ther. 248, 463–469.
Bateson, A. N., Lasham, A. and Darlison, M. G. (1991) γ-Aminobutyric acidA receptor heterogeneity is increased by alternative splicing of a novel β-subunit gene transcript.J. Neurochem. 56, 1437–1440.
Baude, A., Sequier, J. M., McKernan, R. M., Olivier, K. R. and Somogyi, P. (1992) Differential subcellular distribution of the α6 subunit versus the α1 and β2/3 subunits of the GABAA/benzodiazepine receptor complex in granule cells of the cerebellar cortex.Neuroscience 51, 739–748.
Benke D., Fritschy J. M., Trzeciak A., Bannwarth W. and Mohler H. (1994) Distribution, prevalence, and drug binding profile of γ-aminobutyric acid type A receptor subtypes differing in the β-subunit variant.J. Biol. Chem. 269, 27,100–27,107.
Benke D., Mertens S., Trzeciak A., Gillessen D. and Mohler H. (1991) GABAA receptors display association of γ2-subunit with α1- and β2/3-subunits.J. Biol. Chem. 266, 4478–4483.
Benke, D., Mertens S., Trzeciak A., Gillessen D. and Mohler, H. (1991) Identification and immunohis-tocistochemical mapping of GABAA receptor subtypes containing the δ-subunit in rat brain.FEBS Lett. 283, 145–149.
Betz H. (1990) Ligand-gated ion channels in the brain: the amino acid receptor superfamily.Neuron 5, 383–392.
Blair L. A., Levitan E. S., Marshall J., Dionne, V. E. and Barnard, E. A. (1988) Single subunits of the GABAA receptor form ion channels with properties of the native receptor.Science 242, 577–579.
Blanchard, J. C. and Julou, L. (1983) Suriclone: a new cyclopyrrolone derivative recognizing receptors labeled by benzodiazepines in rat hippocampus and cerebellum.J. Neurochem. 40, 601–607.
Bloom F. E. and Iversen L. L. (1971) Localizing3H-GABA in nerve terminals of rat cerebral cortex by electron microscopic autoradiography.Nature 229, 628–630.
Bonetti E. P., Burkhard W. P., Gabl M., Hunkeler W., Lorez H.-P., et al. (1989) Ro 15-4513: partial inverse agonism at the BZR and interactions with ethanol.Pharmacol. Biochem. Behav. 31, 733–749.
Bormann J. (1988) Electrophysiology of GABAA and GABAB receptor subtypes.Trends Neurochem. Sci. 11, 112–116.
Bormann J. and Clapham D. E. (1985) γ-Aminobutyric acid receptor channels in adrenal chromaffin cells: a patch-clamp study.Proc. Natl. Acad. Sci. USA 82, 2168–2172.
Bormann J. and Feigenspan A. (1995) GABAc receptors.Trends Neurosci. 18, 515–519.
Bormann J., Hamill O. P. and Sakmann B. (1987) Mechanism of anion permeation through channels gated by glycine and γ-aminobutyric acid in mouse cultured spinal neurones.J. Physiol. Lond. 385, 243–286.
Bowery N. G. (1993) GABAB receptor pharmacology.Annu. Rev. Pharmacol. Toxicol. 33, 109–147.
Bowery, N. (1989) GABAB receptors and their significance in mammalian pharmacology.Trends Pharmacol. Sci. 10, 401–407.
Bradford H. F. (1995) Glutamate, GABA and epilepsy.Prog. Neurobiol. 47, 477–511.
Braestrup C. and Nielsen M. (1981) [3H]Propyl β-carboline-3-carboxylate as a selective radioligand for the BZ1 benzodiazepine receptor subclass.J. Neurochem. 37, 333–341.
Braestrup, C., Honore, T., Nielsen, M., Petersen, E. N. and Jensen, L. H. (1984) Ligands for benzodiazepine receptors with positive and negative efficacy.Biochem. Pharmacol. 33, 859–862.
Braestrup, C., Nielsen, M., Honore, T., Jensen, L. H. and Petersen, E. N. (1983) Benzodiazepine receptor ligands with positive and negative efficacy.Neuropharmacology 22, 1451–1457.
Braestrup, C., Schmiechen, R., Neef, G., Nielsen, M. and Petersen, E. N. (1982) Interaction of convulsive ligands with benzodiazepine receptors.Science 216, 1241–1243.
Breese G. R., Morrow A. L., Simson P. E., Criswell H. E., McCown T. J., Duncan, G. E. and Keir W. J. (1993) The neuroanatomical specificity of ethanol action on ligand-gated ion channels: a hypothesis.Alcohol. Alcoholism Suppl. 2, 309–313.
Brown M. J. and Bristow D. R. (1996) Molecular mechanisms of benzodiazepine-induced down-regulation of GABAA receptor α1 subunit protein in rat cerebellar granule cells.Br. J. Pharmacol. 118, 1103–1110.
Buhr A., Baur R., Malherbe P. and Sigel E. (1996) Point mutations of the α1β2γ2 γ-aminobutyric acidA receptor affecting modulation of the channel by ligands of the benzodiazepine binding site.Mol. Pharmacol. 49, 1080–1084.
Burgard E. C., Tietz E. I., Neelands T. R. and Macdonald R. L. (1996) Properties of recombinant γ-iminobutyric acidA receptor isoforms containing the α5 subunit subtype.Mol. Pharmacol. 50, 119–127.
Callachan, H., Cottrell, G. A., Hather, N. Y., Lambert, J. J., Nooney, J. M. and Peters, J. A. (1987) Modulation of the GABAA receptor by progesterone metabolites.Proc. R. Soc. Lond. B. Biol. Sci. 231, 359–369.
Caruncho, H. J. and Costa, E. (1994) Double-immunolabelling analysis of GABAA receptor subunits in inlabel-fracture replicas of cultured rat cerebellar granule cells.Rec. Channels 2, 143–153.
Casalotti S. O., Stephenson F. A. and Barnard E. A. (1986) Separate subunits for agonist and benzodiazepine binding in the γ-aminobutyric acidA receptor oligomer.J. Biol. Chem. 261, 15,013–15,016.
Cash D. J. and Subbarao K. (1988) Different effects of pentobarbital on two γ-aminobutyrate receptors from rat brain: channel opening, desensitization, and an additional conformational change.Biochemistry 27, 4580–4590.
Casida J. E. (1993) Insecticide action at the GABA-gated chloride channel: recognition, progress, and prospects.Arch. Insect Biochem. Physiol. 22, 13–23.
Celentano J. J., Gibbs T. T. and Farb D. H. (1988) Ethanol potentiates GABA- and glycine-induced chloride currents in chick spinal cord neurons.Brain Res. 455, 377–380.
Chambon, J. P., Feltz, P., Heaulme, M., Restle, S., Schlichter, R., Biziere, K. and Wermuth, C. G. (1985) An arylaminopyridazine derivative of γ-aminobutyric acid (GABA) is a selective and competitive antagonist at the GABAA receptor site.Proc. Natl. Acad. Sci. USA 82, 1832–1836.
Chang Y. C., Wang R. P., Barot S. and Weiss D. S. (1996) Stoichiometry of a recombinant GABAA receptor.J. Neurosci. 16, 5415–5424.
Cherubini, E., Gaiarsa, J. L. and Ben Ari, Y. (1991) GABA: an excitatory transmitter in early postnatal life.Trends Neurosci. 14, 515–519.
Choi, D. W., Farb D. H. and Fischbach, G. D. (1977) Chlordiazepoxide selectively augments GABA action in spinal cord cell cultures.Nature 269, 342–344.
Choi, D. W., Farb, D. H. and Fischbach, G. D. (1981a) Chloriazepoxide selectively potentiates GABA conductance of spinal cord and sensory neurons in cell culture.J. Neurophysiol. 45, 621–631.
Choi, D. W., Farb D. H. and Fischbach, G. D. (1981b) GABA-mediated synaptic potentials in chick spinal cord and sensory neurons.J. Neurophysiol. 45, 632–643.
Concas A., Santoro G., Serra M., Sanna E. and Biggio G. (1991) Neurochemical action of the general anaesthetic profofol on the chloride ion channel coupled with GABAA receptors.Brain Res. 542, 225–232.
Concas, A., Serra, M., Santoro, G., Maciocco, E., Coccheddu, T. and Biggio, G. (1994) The effect of cyclopyrrolones on GABAA receptor function is different from that of benzodiazepines.Naunyn-Schmied. Arch Pharmacol. 350, 294–300.
Connolly C. N., Wooltorton J. R. A., Smart T. G. and Moss S. J. (1996) Subcellular localization of γ-aminobutyric acid type A receptors is determined by receptor β subunits.Proc. Nat. Acad. Sci. USA 93, 9899–9904.
Connolly, C. N., Krishek, B. J., McDonald, B. J., Smart, T. G. and Moss, S. J. (1996) Assembly and cell surface expression of heteromeric and homomeric γ-aminobutyric acid type A receptors.J. Biol. Chem. 271, 89–96.
Corda M. G., Giorgi O., Longoni B., Ongini E., Montaldo S. and Biggio G. (1988) Preferential affinity of3H-2-oxo-quazepam for type I benzodiazepine recognition sites in the human brain.Life Sci. 42, 189–197.
Corpechot, C., Robel, P., Axelson, M., Sjovall, J. and Baulieu, E. E. (1981) Characterization and measurement of dehydroepiandrosterone sulfate in rat brain.Proc. Natl. Acad. Sci. USA 78, 4704–4707.
Corpechot, C., Synguelakis, M., Talha, S., Axelson, M., Sjovall, J., et al. (1983) Pregnenolone and its sulfate ester in the rat brain.Brain Res. 270, 119–125.
Cottrell, G. A., Lambert, J. J. and Peters, J. A. (1987) Modulation of GABAA receptor activity by alphaxalone.Br. J. Pharmacol. 90, 491–500.
Criswell H. E., Simson P. E., Knapp D. J., Devaud L. L., McCown T. J., et al. (1995) Effect of zolpidem on γ-aminobutyric acid (GABA)-induced inhibition predicts the interaction of ethanol with GABA on individual neurons in several rat brain regions.J. Pharmacol. Exp. Ther. 273, 526–236.
Culiat C. T., Stubbs L. J., Montgomery C. S., Russell L. B. and Rinchik E. M. (1994) Phenotypic consequences of deletion of the γ3, α5, or β3 subunit of the type A γ-aminobutyric acid receptor in mice.Proc. Natl. Acad. Sci. USA 91, 2815–2818.
Culiat, C. T., Stubbs L. J., Woychik R. P., Russell, L. B., Johnson, D. K. and Rinchik E. M. (1995) Deficiency of the β3 subunit of the type A γ-aminobutyric acid receptor causes cleft palate in mice.Nat. Genet. 11, 344–346.
Culiat, C. T., Stubbs, L., Nicholls, R. D., Montgomery, C. S., Russell, L. B., Johnson, D. K. and Rinchik, E. M. (1993) Concordance between isolated cleft palate in mice and alterations within a region including the gene encoding the β3-subunit of the type-A γ-aminobutyric acid receptor.Proc. Natl. Acad. Sci. USA 90, 5105–5109.
Cutting, G. R., Curristin, S., Zoghbi H., O'Hara, B., Seldin M. F. and Uhl, G. R. (1992) Identification of a putative γ-aminobutyric acid (GABA) receptor subunit ρ2 cDNA and colocalization of the genes encoding ρ2 (GABRR2) and ρ1 (GABR1) to human chromosome 6q14-q21 and mouse chromosome 4.Genomics 12, 801–806.
Cutting, G. R., Lu L., Ohara, B. F., Kasch, L. M., Montrose-Rafizadeh, C., et al. (1991) Cloning of the γ-aminobutyric acid (GABA) ρ1 cDNA: a GABA receptor subunit highly expressed in the retina.Proc. Natl. Acad. Sci. USA 88, 2673–2677.
Darlison M. G. and Albrecht B. E. (1995) GABAA Receptor Subtypes: Which, Where and Why.Sem. Neurosci. 7, 115–126.
Davidoff R. A. (1973) Alcohol and presynaptic inhibition in an isolated spinal cord preparation.Arch. Neurol. 28, 60–63.
Davies P. A., Hanna M. C., Hales T. G. and Kirkness E. F. (1997) Insensitivity to anesthetic agents conferred by a class of GABAA receptor subunit.Nature 385, 820–823.
De Deyn P. P., Marescau B. and Macdonald R. L. (1990) Epilepsy and the GABA-hypothesis a brief review and some examples.Acta. Neurol. Belg. 90, 65–81.
DeBlas A. L. (1996) Brain GABAA receptors studied with subunit-specific antibodies.Mol. Neurobiol. 12, 55–71.
Deitrich R. A., Dunwiddie T. V., Harris R. A. and Erwin V. G. (1989) Mechanism of action of ethanol: initial central nervous system actions.Pharmacol. Rev. 41, 489–537.
Deng L., Ransom R. W. and Olsen R. W. (1986) [3H]muscimol photolabels the γ-aminobutyric acid receptor binding site on a peptide subunit distinct from that labeled with benzodiazepines.Biochem. Biophys. Res. Commun. 138, 1308–1314.
Devaud L. L. and Morrow A. L. (1994) Effects of chronic ethanol administration on [3H]zolpidem binding in rat brain.Eur. J. Pharmacol. 267, 243–247.
Devaud L. L., Smith F. D., Grayson D. R. and Morrow A. L. (1995) Chronic ethanol consumption differentially alters the expression of γ-aminobutyric acidA receptor subunit mRNAs in rat cerebral cortex: competitive, quantitative reverse transcriptase-polymerase chain reaction analysis.Mol. Pharmacol. 48, 861–868.
Doble A. and Martin I. L. (1992) Multiple benzodiazepine receptors: no reason for anxiety.Trends Pharmacol. Sci. 13, 76–81.
Dockhorn R. J. and Dockhorn D. W. (1996) Zolpidem in the treatment of short-term insomnia: a randomized, double-blind, placebo-controlled clinical trial.Clin. Neuropharmacol. 19, 333–340.
Draguhn A., Verdron T. A., Ewert M., Seeburg P. H. and Sakmann B. (1990) Functional and molecular distinction between recombinant rat GABAA receptor subtypes by Zn2+.Neuron 5, 781–788.
Drew, C. A. and Johnson, G. A. (1992) Bicucullineand baclofen-insensitive γ-aminobutyric acid binding to rat cerebellar membranes.J. Neurochem. 58, 1087–1092.
Drew, C. A., Johnston, G. A. and Weatherby, R. P. (1984) Bicuculline-insensitive GABA receptors: studies on the binding of (−)-baclofen to rat cerebellar membranes.Neurosci. Lett. 52, 317–321.
Ducic I., Caruncho H. J., Zhu W. J., Vicini S. and Costa E. (1995) γ-Aminobutyric acid gating of C1-channels in recombinant GABAA receptors.J. Pharmacol. Exp. Ther. 272, 438–445.
Ducic I., Puia G., Vicini S. and Costa E. (1993) Triazolam is more efficacious than diazepam in a broad spectrum of recombinant GABAA receptors.Eur. J. Pharmacol. 244, 29–35.
Duncalfe L. L., Carpenter M. R., Smillie L. B., Martin I. L. and Dunn S. M. J. (1996) The major site of photoaffinity labeling of the γ-aminobutyric acid type a receptor by [3H] flunitrazepam is histidine 102 of the α subunit.J. Biol. Chem. 271, 9209–9214.
Duncalfe, L. L. and Dunn, S. M. J. (1996) Mapping of GABAA receptor sites that are photoaffinity-labelled by [H-3] flunitrazepam and [3H]Ro 15-4513.Eur. J. Pharmacol. 298, 313–319.
Ebert B., Wafford K. A., Whitting P. J., Krogsgaard Larsen P. and Kemp J. A. (1994) Molecular pharmacology of γ-aminobutyric acid type A receptor agonists and partial agonists in oocytes injected with different α, β, and γ receptor subunit combinations.Mol. Pharmacol. 46, 957–963.
Enz, R., Brandstatter, J. H., Hartveit, E., Wassle, H. and Bormann, J. (1995) Expression of GABA receptor rho 1 and rho 2 subunits in the retina and brain of the rat.Eur. J. Neurosci. 7, 1495–1501.
Evoniuk, G., Moody, E. J. and Skolnick, P. (1989) Ultraviolet irradiation selectively disrupts the γ-aminobutyric acid/benzodiazepine receptor-linked chloride ionophore.Mol. Pharmacol. 35, 695–700.
Facklam, M., Schoch, P. and Haefely, W. E. (1992) Relationship between benzodiazepine receptor occupancy and potentiation of γ-aminobutyric acid-stimulated chloride flux in vitro of four ligands of differing intrinsic efficacies.J. Pharmacol. Exp. Ther. 261, 1106–1112.
Faure Halley C., Graham D., Arbilla S. and Langer S. Z. (1993) Expression and properties of recombinant α1β2γ2 and α5β2γ2 forms of the rat GABAA receptor.Eur. J. Pharmacol. 246, 283–287.
Feigenspan A. and Bormann J. (1994) Differential pharmacology of GABAA and GABAC receptors on rat retinal bipolar cells.Eur. J. Pharmacol. 288, 97–104.
Feigenspan A., Wassle H. and Bormann J. (1993) Pharmacology of GABA receptor Cl− channels in rat retinal bipolar cells.Nature 361, 159–162.
Franks N. P. and Lieb W. R. (1994) Molecular and cellular mechanisms of general anaesthesia.Nature 367, 607–614.
Fraser A. D. (1996) New drugs for the treatment of epilepsy.Clin. Biochem. 29, 97–110.
Freund R. K. and Palmer M. R. (1996) 8-Bromo-cAMP mimics β-adrenergic sensitization of GABA responses to ethanol in cerebellar Purkinje neurons in vivo.Alcoholism-Clin. Exp. Res. 20, 408–412.
Fritschy J. M. and Mohler H. (1995) GABAA-receptor heterogeneity in the adult rat brain: differential regional and cellular distribution of seven major subunits.J. Comp. Neurol. 359, 154–194.
Fritschy J. M., Benke D., Mertens S., Oertel W. H., Bachi T. and Mohler, H. (1992) Five subtypes of type A γ-aminobutyric acid receptors identified in neurons by double and triple immunofluorescence staining with subunit-specific antibodies.Proc. Natl. Acad. Sci. USA 89, 6726–6730.
Fritschy, J. M., Paysan, J., Enna, A. and Mohler, H. (1994) Switch in the expression of rat GABAA-receptor subtypes during postnatal development: an immunohistochemical study.J. Neurosci. 14, 5302–5324.
Gage P. W. and Robertson B. (1995) Prolongation of inhibitory postsynaptic currents by pentobarbitone, halothane and ketamine in CA1 pyramidal cells in rat hippocampus.Br. J. Pharmacol. 85, 675–681.
Gallagher J. P., Nakamura J. and Shinnick Gallagher P. (1983) The effects of temperature, pH and Cl-pump inhibitors on GABA responses recorded from cat dorsal root ganglia.Brain Res. 267, 249–259.
Gao B., Fritschy J. M., Benke D. and Mohler H. (1993) Neuron-specific expression of GABAA-receptor subtypes: differential association of the α1- and α3-subunits with serotonergic and GABAergic neurons.Neuroscience 54, 881–892.
Gao B., Hornung J. P. and Fritschy J. M. (1995) Identification of distinct GABAA-receptor subtypes in cholinergic and parvalbumin-positive neurons of the rat and marmoset medial septum-diagonal band complex.Neuroscience 65, 101–117.
Gee K. W. (1987) Phenylquinolines PK 8165 and PK 9084 allosterically modulate [35S]t-butylbicyclophosphorothionate binding to a chloride ionophore in rat brain via a novel Ro5-4864 binding site.J. Pharmacol. Exp. Ther. 240, 747–753.
Gee K. W., Brinton R. E. and McEwen B. S. (1988) Regional distribution of a Ro5 4864 binding site that is functionally coupled to the γ-aminobutyric acid/benzodiazepine receptor complex in rat brain.J. Pharmacol. Exp. Ther. 244, 379–383.
Gee, K. W. (1988) Steroid modulation of the GABA/benzodiazepine receptor-linked chloride ionophore.Mol. Neurobiol. 2, 291–317.
Gee, K. W., Bolger, M. B., Brinton, R. E., Coirini, H. and McEwen, B. S. (1988) Steroid modulation of the chloride ionophore in rat brain: structure-activity requirements, regional dependence and mechanism of action.J. Pharmacol. Exp. Ther. 246, 803–812.
Gingrich K. J., Roberts W. A. and Kass R. S. (1995) Dependence of the GABAA receptor gating kinetics on the α-subunit isoform: implications for structure-function relations and synaptic transmission.J. Physiol Lond 489, 529–543.
Glass M. and Dragunow M. (1995) Neurochemical and morphological changes associated with human epilepsy.Brain Res. Rev. 21, 29–41.
Granger P., Biton B., Faure C., Vige X., Depoortere H., et al. (1995) Modulation of the γ-aminobutyric acid type A receptor by the antiepileptic drugs carbamazepine and phenytoin.Mol. Pharmacol. 47, 1189–1196.
Gray R. and Johnston D. (1985) Rectification of single GABA-gated chloride channels in adult hippocampal neurons.J. Neurophysiol. 54, 134–142.
Greger R. and Wangemann P. (1987) Loop diuretics.Renal Physiol. 10, 174–183.
Gunther U., Benson J., Benke D., Fritschy J. M., Reyes G. et al. (1995) Benzodiazepine-insensitive mice generated by targeted disruption of the γ2 subunit gene of γ-aminobutyric acid type A receptors.Proc. Natl. Acad. Sci. USA 92, 7749–7753.
Gurley D., Amin J., Ross P. C., Weiss D. S. and White G. (1995) Point mutations in the M2 region of the α, β, or γ subunit of the GABAA channel that abolish block by picrotoxin.Rec. Channels 3, 13–20.
Gutierrez A., Khan Z. U. and De Blas A. L. (1994) Immunocytochemical localization of γ2 short and γ2 long subunits of the GABAA receptor in the rat brain.J. Neurosci. 14, 7168–7179.
Gutierrez A., Khan Z. U. and DeBlas, A. L. (1996) Immunocytochemical localization of the α(6) subunit of the γ-aminobutyric AcidA receptor in the rat nervous system.J. Comp. Neurol. 365, 504–510.
Hadingham K. L., Wafford K. A., Thompson S. A., Palmer K. J. and Whiting P. J. (1995) Expression and pharmacology of human GABAA receptors containing γ3 subunits.Eur. J. Pharmacol.-Molec. Pharm. 291, 301–309.
Hadingham K. L., Wingrove P. B., Wafford K. A., Bain C., Kemp J. A. et al. (1993) Role of the β subunit in determining the pharmacology of human γ-aminobutyric acid type A receptors [published erratum appears inMol. Pharmacol. 1994 Jul;46(1):211].Mol. Pharmacol. 44, 1211–1218.
Hadingham K. L., Wingrove P., Le Bourdelles B., Palmer K. J., Ragan C. I. and Whiting P. J. (1993) Cloning of cDNA sequences encoding human α2 and α3 γ-aminobutyric acidA receptor subunits and characterization of the benzodiazepine pharmacology of recombinant α1-, α2-, α3-, and α5-containing human γ-aminobutyric acidA receptors.Mol. Pharmacol. 43, 970–975.
Haefely, W. (1985) Pharmacology of benzodiazepine antagonists.Pharmacopsychiatry 18, 163–166.
Halasy K. and Somogyi P. (1993) Distribution of GABAergic synapses and their targets in the dentate gyrus of rat: a quantitative immunoelectron microscopic analysis.J. Hirnforsch. 34, 299–308.
Hales T. G. and Lambert J. J. (1991) The actions of propofol on inhibitory amino acid receptors of bovine adrenomedullary chromaffin cells and rodent central neurones.Br. J. Pharmacol. 104, 619–628.
Hales, T. G. and Tyndale, R. F. (1994) Few cell lines with GABAA mRNAs have functional receptors.J. Neurosci. 14, 5429–5436.
Hall A. C., Lieb W. R. and Franks N. P. (1994) Stereoselective and non-stereoselective actions of isoflurane on the GABAA receptor.Br. J. Pharmacol. 112, 906–910.
Hamann M., Desarmenien M., Vanderheyden P., Piguet P. and Feltz P. (1990) Electrophysiological study of tert-butylbicyclophosphorothionate-induced block of spontaneous chloride channels.Mol. Pharmacol. 37, 578–582.
Harris B. D., Moody E. J., Gu Z. Q. and Skolnick P. (1995) Contribution of “diazepam-insensitive” GABAA receptors to the alcohol antagonist properties of ro 15-4513 and related imidazobenzodiazepines.Pharmacol. Biochem. Behav. 52, 113–118.
Harris B., Wong G. and Skolnick P. (1993) Neurochemical actions of inhalational anesthetics at the GABAA receptor complex.J. Pharmacol. Exp. Ther. 265, 1392–1398.
Harris R. A., McQuilkin S. J., Paylor R., Abeliovich A., Tonegawa S. and Wehner J. M. (1995) Mutant mice lacking the γ isoform of protein kinase C show decreased behavioral actions of ethanol and altered function of γ-aminobutyrate type A receptors [see comments].Proc. Natl. Acad. Sci. USA 92, 3658–3662.
Harris R. A., Mihic S. J., Dildymayfield J. E. and Machu T. K. (1995) Actions of anethetics on ligand-gated ion channels: Role of receptor subunit composition.FASEB J. 9, 1454–1462.
Harris R. A., Proctor W. R., McQuilkin S. J., Klein R. L., Mascia M. P., et al. (1995) Ethanol increases GABAA responses in cells stably transfected with receptor subunits.Alcohol. Clin. Exp. Res. 19, 226–232.
Harrison N. L., Kugler J. L., Jones M. V., Greenblatt E. P. and Pritchett D. B. (1993) Positive modulation of human γ-aminobutyric acid type A and glycine receptors by the inhalation anesthetic isoflurane.Mol. Pharmacol. 44, 628–632.
Harrison, N. L. and Simmonds, M. A. (1984) Modulation of the GABA receptor complex by a steroid anaesthetic.Brain Res. 323, 287–292.
Harrison, N. L., Majewska, M. D., Harrington, J. W. and Barker, J. L. (1987) Structure-activity relationships for steroid interaction with the γ-aminobutyric acidA receptor complex.J. Pharmacol. Exp. Ther. 241, 346–353.
Harrison, N. L., Vicini, S. and Barker, J. L. (1987) A steroid anesthetic prolongs inhibitory postsynaptic currents in cultured rat hippocampal neurons.J. Neurosci. 7, 604–609.
Harvey, R. J., Chinchetru, M. A. and Darlison M. G. (1994) Alternative splicing of a 51-nucleotide exon that encodes a putative protein kinase C phosphorylation site generates two forms of the chicken γ-aminobutyric acidA receptor β2 subunit.J. Neurochem. 62, 10–16.
Hattori, K., Akaike, N., Oomura, Y. and Kuraoka, S. (1984) Internal perfusion studies demonstrating GABA-induced chloride responses in frog primary afferent neurons.Am. J. Physiol. 246, C259–265.
Hattori, K., Oomura, Y. and Akaike, N. (1986) Diazepam action on γ-aminobutyric acid-activated chloride currents in internally perfused frog sensory neurons.Cell. Mol. Neurobiol. 6, 307–323.
Hauser C. A., Chesnoy Marchais D., Robel P. and Baulieu E. E. (1995) Modulation of recombinant α 6β2γ2 GABAA receptors by neuroactive steroids.Eur. J. Pharmacol. 289, 249–257.
Heaulme, M., Chambon J. P., Leyris, R., Wermuth, C. G. and Biziere, K. (1987) Characterization of the binding of [3H]SR 95531, a GABAA antagonist, to rat brain membranes.J. Neurochem. 48, 1677–1686.
Herb, A., Wisden, W., Lüddens, H., Puia, G., Vicini, S. and Seeburg, P. H. (1992) The third γ subunit of the γ-aminobutyric acid type A receptor family.Proc. Natl. Acad. Sci. USA 89, 1433–1437.
Herblin W. F. and Mechem C. C. (1984) Short-wave ultraviolet irradiation increases photo-affinity labeling of benzodiazepine sites.Life Sci. 35, 317–324.
Horne A. L., Harkness P. C., Hadingham K. L., Whitting P. and Kemp J. A. (1993) The influence of the γ2L subunit on the modulation of responses to GABAA receptor activation.Br. J. Pharmacol. 108, 711–716.
Hunt, P. and Clements Jewery, S. (1981) A steroid derivative, R 5135, antagonizes the GABA/benzodiazepine receptor interaction.Neuropharmacology 20, 357–361.
Im H. K., Im W. B., Hamilton B. J., Carter D. B. and Vonvoigtlander P. F. (1993) Potentiation of γ-aminobutyric acid-induced chloride currents by various benzodiazepine site agonists with the α1γ2, β2γ2 and α1β2γ2 subtypes of cloned γ-aminobutyric acid type A receptors.Mol. Pharmacol. 44, 866–870.
Im H. K., Im, W. B., Carter D. B. and McKinley D. D. (1995) Interaction of β-carboline inverse agonists for the benzodiazepine site with another site on GABAA receptors.Br. J. Pharmacol. 114, 1040–1044.
Im M. S., Hamilton B. J., Carter D. B. and Im W. B. (1992) Selective potentiation of GABA-mediated Cl− current by lanthanum ion in subtypes of cloned GABAA receptors.Neurosci. Lett. 144, 165–168.
Im W. B. and Blakeman D. P. (1991) Correlation between γ-aminobutyric acidA receptor ligand-induced changes in t-butylbicyclophosphoro[35S] thionate binding and36CI- uptake in rat cerebrocortical membranes.Mol. Pharmacol. 39, 394–398.
Im W. B., Im H. K., Pregenzer J. F., Hamilton B. J., Carter D. B. et al. (1993) Differential affinity of dihydroimidazoquinoxalines and diimidazoquinazolines to the α1β2γ2 and α6β2γ2 subtypes of cloned GABAA receptors.Br. J. Pharmacol. 110, 677–680.
Im, W. B., Blakeman, D. P., Davis, J. P. and Ayer D. E. (1990) Studies on the mechanism of interactions between anesthetic steroids and γ-aminobutyric acidA receptors.Mol. Pharmacol. 37, 429–434.
Inomata N., Ishihara T. and Akaike N. (1988) Effects of diuretics on GABA-gated chloride current in frog isolated sensory neurones.Br. J. Pharmacol. 93, 679–683.
Inomata N., Tokutomi N., Oyama Y. and Akaike N. (1988) Intracellular picrotoxin blocks pentobarbital-gated Cl- conductance.Neurosci. Res. 6, 72–75.
Inoue M. and Akaike N. (1988) Blockade of γ-aminobutyric acid-gated chloride current in frog sensory neurons by picrotoxin.Neurosci. Res. 5 380–394.
Jackson M. B., Lecar H., Mathers D. A. and Barker J. L. (1982) Single channel currents activated by γ-aminobutyric acid, muscimol, and (−)-pentobarbital in cultured mouse spinal neurons.J. Neurosci. 2, 889–894.
Johnston, G. A., Curtis, D. R., Beart, P. M., Game C. J., McCulloch, R. M. and Twitchin, B. (1975) Cis-and trans-4-aminocrotonic acid as GABA analogues of restricted conformation.J. Neurochem. 24, 157–160.
Jones M. V. and Harrison N. L. (1993) Effects of volatile anesthetics on the kinetics of inhibitory postsynaptic currents in cultured rat hippocampal neurons.J. Neurophysiol. 70, 1339–1349.
Jones M. V. and Westbrook G. L. (1995) Desensitized states prolong GABAA channel responses to brief agonist pulses.Neuron 15, 181–191.
Jones M. V., Harrison N. L., Pritchett D. B. and Hales T. G. (1995) Modulation of the GABAA receptor by propofol is independent of the γ subunit.J. Pharmacol. Exper. Therap. 274, 962–968.
Jones, A., Korpi, E. R., McKernan, R. M., Nusser, A., Pelz R. et al. (1997) Ligand-gated ion channel subunit partnerships: GABAA receptor γ6 subunit gene inactivation inhibits δ subunit expression.J. Neurosci. (Submitted)
Joyce K. A., Atkinson A. E., Bermudez I., Beadle D. J. and King L. A. (1993) Synthesis of functional GABAA receptors in stable insect cell lines.FEBS Lett. 335, 61–64.
Kardos, J. and Cash, D. J. (1990) Transmembrane 36Cl-flux measurements and desensitization of the γ-aminobutyric acidA receptor.J. Neurochem. 55, 1095–1099.
Karlin A. and Akabas M. H., (1995) Toward a structural basis for the function of nicotinic acetylcholine receptors and their cousins.Neuron 15, 1231–1244.
Karobath M., Drexler G. and Supavilai P. (1981) Modulation by picrotoxin and IPTBO of3H-flunitrazepam binding to the GABA/benzodiazepine receptor complex of rat cerebellum.Life Sci. 28, 307–313.
Karobath, M. and Sperk, G. (1979) Stimulation of benzodiazepine receptor binding by γ-aminobutyric acid.Proc. Natl. Acad. Sci. USA 76, 1004–1006.
Kato K. (1990) Novel GABAA receptor α subunit is expressed only in cerebellar granule cells.J. Mol. Biol. 214, 619–624.
Kaupmann K., Huggel K., Heid J., Flor P. J., Bischoff S. et al. (1997) Expression cloning of GABAB receptors uncovers similarity to metabotropic glutamate receptors.Nature 386, 239–246.
Kerr D. I. B. and Ong J. (1995) GABAB receptors.Pharmacol. Ther. 67, 187–246.
Khan Z. U., Gutierrez A. and De Blas A. L. (1994) The subunit composition of a GABAA benzodiazepine receptor from rat cerebellum.J. Neurochem. 63, 371–374.
Khrestchatisky M., MacLennan A. J., Chiang M. Y., Xu W. T., Jackson M. B., et al. (1989) A novel α subunit in rat brain GABAA receptors.Neuron 3, 745–753.
Kirkness, E. F. and Fraser, C. M. (1993) A strong promoter element is located between alternative exons of a gene encoding the human γ-aminobutyric acid-type A receptor β3 subunit (GABRB3).J. Biol. Chem. 268, 4420–4428.
Kleingoor, C., Ewert M., von Blankenfeld G., Seeburg P. H. and Kettenmann H. (1991) Inverse but not full benzodiazepine agonists modulate recombinant α6 β2 γ2 GABAA receptors in transfected human embryonic kidney cells.Neurosci. Lett. 130, 169–172.
Kleingoor C., Wieland H. A., Korpi E. R., Seeburg P. H. and Kettenmann H. (1993) Current potentiation by diazepam but not GABA sensitivity is determined by a single histidine residue.Neuroreport 4, 187–190.
Knoflach, F., Benke D., et al. (1996) Pharmacological modulation of the diazepam-insensitive recombinant γ-aminobutyric acidA receptors α4 β2 γ2 and α6 β2 γ2.Mol. Pharmacol. 50, 1253–1261.
Knoflach, F., Drescher, U., Scheurer, L., Malherbe, P. and Mohler, H. (1993) Full and partial agonism displayed by benzodiazepine receptor ligands at recombinant γ-aminobutyric acidA receptor subtypes.J. Pharmacol. Exp. Ther. 266, 385–391.
Knoflach, F., Rhyner, T., Villa, M., Kellenberger, S., Drescher, U., et al. (1991) The γ3-subunit of the GABAA receptor confers sensitivity to benzodiazepine receptor ligands.FEBS Lett. 293, 191–194.
Kofuji, P., Wang, J. B., Moss, S. J., Huganir, R. L. and Burt, D. R. (1991) Generation of two forms of the γ- aminobutyric acidA receptor γ2-subunit in mice by alternative splicing.J. Neurochem. 56, 713–715.
Kokate, T. G., Svensson, B. E. and Rogawski, M. A. (1994) Anticonvulsant activity of neurosteroids: correlation with γ-aminobutyric acid-evoked chloride current potentiation.J. Pharmacol. Exp. Ther. 270, 1223–1229.
Korpi E. R. (1994) Role of GABAA receptors in the actions of alcohol and alcoholism: recent advances.Alcohol. Alcoholism 29, 115–129.
Korpi E. R. and Lüddens H. (1993) Regional γ-aminobutyric acid sensitivity of t-butylbicyclophosphoro [35S]thionate binding depends on γ-aminobutyric acidA receptor α subunit.Mol. Pharmacol. 44, 87–92.
Korpi E. R. and Lüddens H. (1997) Furosemide interactions with brain GABAA receptors.Br. J. Pharmacol. 120, 741–748.
Korpi E. R., Kleingoor C., Kettenmann H. and Seeburg P. H. (1993) Benzodiazepine-induced motor impairment linked to point mutation in cerebellar GABAA receptor.Nature 361, 356–359.
Korpi E. R., Kuner T., Seeburg P. H., and Lüddens H. (1995) Selective antagonist for the cerebellar granule cell-specific γ-aminobutyric acid type A receptor.Mol. Pharmacol. 47, 283–289.
Korpi, E. R., Kuner, T., Kristo, P., Köhler, M., Herb, A., Lüddens, H. and Seeburg, P. H. (1994) Small N-terminal deletion by splicing in cerebellar α6 subunit abolishes GABAA receptor function.J. Neurochem. 63, 1167–1170.
Krishek B. J., Moss S. J. and Smart T. G. (1996) Homomeric β 1 γ-aminobutyric acidA receptorion channels: evaluation of pharmacological and physiological properties.Mol. Pharmacol. 49, 494–504.
Krogsgaard Larsen, P., Frolund, B., Jorgensen, F. S. and Schousboe, A. (1994) GABAA receptor agonists, partial agonists, and antagonists. Design and therapeutic prospects.J. Med. Chem. 37, 2489–2505.
Kusama T., Spivak C. E., Whiting P., Dawson V. L., Schaeffer J. C. and Uhl G. R. (1993a) Pharmacology of GABA ρ1 and GABA α/β receptors expressed inXenopus oocytes and COS cells.Br. J. Pharmacol. 109, 200–206.
Kusama T., Wang T. L., Guggino W. B., Cutting G. R. and Uhl G. R. (1993b) GABA ρ2 receptor pharmacological profile: GABA recognition site similarities to ρ1.Eur. J. Pharmacol. 245, 83–84.
Lüddens H. and Korpi E. (1996) GABAA receptors: pharmacology, behavioral, roles and motor disorders.Neuroscientist 2, 15–23.
Lüddens H. and Korpi E. R. (1995) GABA antagonists differentiate between recombinant GABAA/benzodiazepine receptor subtypes.J. Neurosci. 15, 6957–6962.
Lüddens H. and Wisden W. (1991) Function and pharmacology of multiple GABAA receptor subunits.Trends Pharmacol. Sci. 12, 49–51.
Lüddens H., Seeburg P. H. and Korpi E. R. (1994) Impact of β and γ variants on ligand-binding properties of γ-aminobutyric acid type A receptors.Mol. Pharmacol. 45, 810–814.
Lüddens, H., Pritchett D. B., Kohler, M., Killisch I., Keinanen, K. et al. (1990) Cerebellar GABAA receptor selective for a behavioural alcohol antagonist.Nature 346, 648–651.
Lambert J. J., Peters J. A., Sturgess N. C. and Hales T. G. (1990) Steroid modulation of the GABAA receptor complex: electrophysiology studies.Ciba Found. Symp. 153, 56–71.
Laurie D. J., Seeburg P. H. and Wisden W. (1992) The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. II. Olfactory Bulb and Cerebellum.J. Neurosci. 12, 1063–1076.
Laurie D. J., Wisden W. and Seeburg P. H. (1992) The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development.J. Neurosci. 12, 4151–4172.
Lawrence L.J. and Casida J. E. (1984) Interactions of lindane, toxaphene and cyclodienes with brain-specific t-butylbicyclophosphorothionate receptor.Life Sci. 35, 171–178.
Leeb Lundberg F., Snowman A. and Olsen R. W. (1980) Barbiturate receptor sites are coupled to benzodiazepine receptors.Proc. Natl. Acad. Sci. USA 77, 7468–7472.
Leeb Lundberg F., Snowman A. and Olsen R. W. (1981) Interaction of anticonvulsants with the barbiturate-benzodiazepine-GABA receptor complex.Eur. J. Pharmacol. 72, 125–129.
Leeb Lundberg F., Snowman A., and Olsen R. W. (1981) Perturbation of benzodiazepine receptor binding by pyrazolopyridines involves picrotoxinin/barbiturate receptor sites.J. Neurosci. 1, 471–477.
Leidenheimer, N. J., Browning, M. D. and Harris, R. A. (1991) GABAA receptor phosphorylation: multiple sites, actions and artifacts.Trends Pharmacol. Sci. 12, 84–87.
Levitan E. S., Blair L. A., Dionne V. E. and Barnard, E. A. (1988) Biophysical and pharmacological properties of cloned GABAA receptor subunits expressed inXenopus oocytes.Neuron 1, 773–781.
Levitan E. S., Schofield P. R., Burt D. R., Rhee L. M., Wisden W. et al. (1988) Structural and functional basis for GABAA receptor heterogeneity.Nature 335, 76–79.
Lin A. M., Bickford P. C. and Palmer M. R. (1993) The effects of ethanol on γ-aminobutyric acid-induced depressions of cerebellar Purkinje neurons: influence of β adrenergic receptor action in young and aged Fischer 344 rats.J. Pharmacol. Exp. Ther. 264, 951–957.
Lin A. M., Freund R. K. and Palmer M. R. (1993) Sensitization of γ-aminobutyric acid-induced depression of cerebellar Purkinje neurons to the potentiative effects of ethanol by β adrenergic mechanisms in rat brain.J. Pharmacol. Exp. Ther. 265, 426–432.
Lin L. H., Chen L. L., Zirrolli J. A. and Harris R. A. (1992) General anesthetics potentiate γ-aminobutyric acid actions on γ-aminobutyric acidA receptors expressed byXenopus oocytes: lack of involvement of intracellular calcium.J. Pharmacol. Exp. Ther. 263, 569–578.
Lin Y. F., Angelotti T. P., Dudek E. M., Browning M. D. and Macdonald R. L. (1996) Enhancement of recombinant α1β1γ2L γ-aminobutyric acidA receptor whole-cell currents by protein kinase C is mediated through phosphorylation of both β1 and γ2L subunits.Mol. Pharmacol. 50, 185–195.
Liu D. T., Tibbs G. R. and Siegelbaum S. A. (1996) Subunit stoichiometry of cyclic nucleotide-gated channels and effects of subunit order on channel function.Neuron 16, 983–990.
Liu R., Hu R. J., Zhang P., Skolnick P. and Cook J. M. (1996) Synthesis and pharmacological properties of novel 8-substituted imidazobenzodiazepines: high-affinity, selective probes for α 5-containing GABAA receptors.J Med Chem 39, 1928–1934.
Lloyd, G. K., Danielou, G. and Thuret, F. (1990) The activity of zolpidem and other hypnotics within the γ-aminobutyric acid (GABAA) receptor supramolecular complex, as determined by35S-t-butylbicyclophosphorothionate (35S-TBPS) binding to rat cerebral cortex membranes.J. Pharmacol. Exp. Ther. 255, 690–696.
Lo M. M., Strittmatter S. M. and Snyder S. H. (1982) Physical separation and characterization of two types of benzodiazepine receptors.Proc. Natl. Acad. Sci. USA 79, 680–684.
Lolait, S. J., AM, O. C., Kusano, K. and Mahan, L. C. (1989) Pharmacological characterization and region-specific expression in brain of the β2- and β-3-subunits of the rat GABAA receptor.FEBS Lett. 258, 17–21.
Longoni B. and Olsen R. W. (1992) Studies on the mechanism of interaction of anesthetics with GABA-A receptors.Adv. Biochem. Psychopharmacol. 47, 365–378.
Longoni B., Demontis G. C. and Olsen R. W. (1993) Enhancement of γ-aminobutyric acidA receptor function and binding by the volatile anesthetic halothane.J. Pharmacol. Exp. Ther. 266, 153–159.
Möhler H., Malherbe P., Draguhn A. and Richards J. G. (1990) GABAA-receptors: structural requirements and sites of gene expression in mammalian brain.Neurochem. Res. 15, 199–207.
Macdonald R. L. (1995) Ethanol, γ-aminobutyrate type A receptors, and protein kinase C phosphorylation [comment].Proc. Natl. Acad. Sci. USA 92, 3633–3635.
Macdonald R. L. and Barker J. L. (1978) Different actions of anticonvulsant and anesthetic barbiturates revealed by use of cultured mammalian neurons.Science 200, 775–777.
Macdonald R. L. and Olsen R. W. (1994) GABAA receptor channels.Annu. Rev. Neurosci. 17, 569–602.
Macdonald R. L. and Twyman R. E. (1992) Kinetic properties and regulation of GABAA receptor channels.Ion Channels 3, 315–343.
Macdonald R. L., Rogers C. J. and Twyman R. E. (1989) Barbiturate regulation of kinetic properties of the GABAA receptor channel of mouse spinal neurones in culture.J. Physiol. Lond. 417, 483–500.
Macdonald R. L., Rogers C. J. and Twyman R. E. (1989) Kinetic properties of the GABAA receptor main conductance state of mouse spinal cord neurones in culture.J. Physiol. Lond. 410, 479–499.
Macdonald R. L., Twyman, R. E., Ryan Jastrow, T. and Angelotti, T. P. (1992) Regulation of GABAA receptor channels by anticonvulsant and convulsant drugs and by phosphorylation.Epilepsy Res. Suppl. 9, 265–277.
Macdonald, R. and Barker, J. L. (1978) Benzodiazepines specifically modulate GABA-mediated postsynaptic inhibition in cultured mammalian neurones.Nature 271, 563–564.
MacIver M. B., Tanelian D. L. and Mody I. (1991) Two mechanisms for anesthetic-induced enhancement of GABAA-mediated neuronal inhibition.Ann. NY Acad. Sci. 625, 91–96.
Maconochie, D. J., Zempel, J. M. and Steinbach, J. H. (1994) How quickly can GABAA receptors open?Neuron 12, 61–71.
Majewska M. D. (1988) Interaction of ethanol with the GABAA receptor in the rat brain: possible involvement of endogenous steroids.Alcohol 5, 269–273.
Majewska M. D. and Schwartz R. D. (1987) Pregnenolone-sulfate: an endogenous antagonist of the γ-aminobutyric acid receptor complex in brain?Brain Res. 404, 355–360.
Majewska M. D., Bisserbe J. C. and Eskay R. L. (1985) Glucocorticoids are modulators of GABAA receptors in brain.Brain Res. 339, 178–182.
Majewska M. D., Mienville J. M. and Vicini S. (1988) Neurosteroid pregnenolone sulfate antagonizes electrophysiological responses to GABA in neurons.Neurosci. Lett. 90, 279–284.
Majewska, M. D. (1992) Neurosteroids: endogenous bimodal modulators of the GABAA receptor. Mechanism of action and physiological significance.Prog. Neurobiol. 38, 379–395.
Majewska, M. D., Harrison, N. L., Schwartz, R. D., Barker, J. L. and Paul, S. M. (1986) Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor.Science 232, 1004–1007.
Maksay G. (1994) Thermodynamics of γ-aminobutyric acid type A receptor binding differentiate agonists from antagonists.Mol. Pharmacol. 46, 386–390.
Maksay G. and Simonyi M. (1985) Benzodiazepine anticonvulsants accelerate and β-carboline convulsants decelerate the kinetics of [35S]TBPS binding at the chloride ionophore.Eur. J. Pharmacol. 117, 275–278.
Maksay G. and Simonyi M. (1986) Kinetic regulation of convulsant (TBPS) binding by GABAergic agents.Mol. Pharmacol. 30, 321–328.
Maksay G. and Simonyi M. (1988) Nonequilibrium modulation of [35S]-TBPS binding by benzodiazepine agonists and antagonists.Biochem. Pharmacol. 37, 2195–2200.
Maksay G. and Ticku M. K. (1985) GABA, depressants and chloride ions affect the rate of dissociation of [35S]-t-butylbicyclophosphorothionate binding.Life Sci. 37, 2173–2180.
Maksay G. and van Rijn C. M. (1993) Interconvertible kinetic states of t-butylbicycloorthobenzoate binding sites of the γ-aminobutyric acidA ionophores.J. Neurochem. 61, 2081–2088.
Malatynska E., Giroux M. L., Dilsaver S. C. and Schwarzkopf S. B. (1992) Bidirectional effect of β-carboline agonists at the benzodiazepine-GABAA receptor chloride ionophore complex on GABA-stimulated36CI-uptake.Brain Res. Bull. 28, 605–611.
Malherbe P., Draguhn A., Multhaup G., Beyreuther K. and Möhler H. (1990) GABAA-receptor expressed from rat brain α- and β-subunit cDNAs displays potentiation by benzodiazepine receptor ligands.Mol. Brain Res. 8, 199–208.
Malherbe P., Sigel E., Baur R., Persohn E., Richards J. G. and Möhler H. (1990a) Functional characteristics and sites of gene expression of the α1, β1, γ2-isoform of the rat GABAA receptor.J. Neurosci. 10, 2330–2337.
Malherbe P., Sigel E., Baur R., Persohn E., Richards J. G. and Möhler H. (1990b) Functional expression and sites of gene transcription of a novel α subunit of the GABAA receptor in rat brain.FEBS Lett. 260, 261–265.
Marszalec W., Kurata Y., Hamilton B. J., Carter D. B. and Narahashi T. (1994) Selective effects of alcohols on γ-aminobutyric acidA receptor subunits expressed in human embryonic kidney cells.J. Pharmacol. Exp. Ther. 269, 157–163.
Martin I. L. and Doble A. (1983) The benzodiazepine receptor in rat brain and its interaction with ethyl β-carboline-3-carboxylate.J. Neurochem. 40, 1613–1619.
Martin J. V., Williams D. B., Fitzgerald R. M., Im H. K. and Vonvoigtlander P. F. (1996) Thyroid hormonal modulation of the binding and activity of the GABAA receptors complex of brain.Neuroscience 73, 705–713.
Mathers D. A. (1985) Spontaneous and GABA-induced single channel currents in cultured murine spinal cord neurons.Can. J. Physiol. Pharmacol. 63, 1228–1233.
McEwen, B. S. and Parsons, B. (1982) Gonadal steroid action on the brain: neurochemistry and neuropharmacology.Annu. Rev. Pharmacol. Toxicol. 22, 555–598.
Mertens, S., Benke, D. and Mohler, H. (1993) GABAA receptor populations with novel subunit combinations and drug binding profiles identified in brain by α5- and δ-subunit-specific immunopurification.J. Biol. Chem. 268, 5965–5973.
Mhatre M. C., Pena G., Sieghart W. and Ticku M. K. (1993) Antibodies specific for GABAA receptor α subunits reveal that chronic alcohol treatment down-regulates α-subunit expression in rat brain regions.J. Neurochem. 61, 1620–1625.
Michelson, H. B. and Wong, R. K. (1991) Excitatory synaptic responses mediated by GABAA receptors in the hippocampus.Science 253, 1420–1423.
Mienville J. M. and Vicini S. (1989) Pregnenolone sulfate antagonizes GABAA receptor-mediated currents via a reduction of channel opening frequency.Brain Res. 489, 190–194.
Mihic S. J., Sanna E., Whiting P. J. and Harris R. A. (1995) Pharmacology of recombinant GABAA receptors.GABA A Receptors and Anxiety48, 17–40.
Mihic S. J., Whiting P. J. and Harris R. A. (1994) Anaesthetic concentrations of alcohols potentiate GABAA receptor-mediated currents: lack of subunit specificity.Eur. J. Pharmacol. 268, 209–214.
Mihic S. J., Whiting P. J., Klein R. L., Wafford K. A. and Harris R. A. (1994) A single amino acid of the human γ-aminobutyric acid type A receptor γ2 subunit determines benzodiazepine efficacy.J. Biol. Chem. 269, 32,768–32,773.
Misgeld U., Bijak M. and Jarolimek W. (1995) A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system.Prog. Neurobiol. 46, 423–462.
Misgeld U., Deisz R. A., Dodt H. U. and Lux H. D. (1986) The role of chloride transport in postsynaptic inhibition of hippocampal neurons.Science 232, 1413–1415.
Mohler H., Burkard, W. P., Keller, H. H., Richards, J. G. and Haefely, W. (1981) Benzodiazepine antagonist Ro 15 1788: binding characteristics and interaction with drug-induced changes in dopamine turnover and cerebellar cGMP levels.J. Neurochem. 37, 714–722.
Mohler, H. and Okada, T. (1977) Properties of3H-diazepam binding to benzodiazepine receptors in rat cerebral cortex.Life Sci. 20, 2101–2110.
Morrow, A. L., Suzdak, P. D. and Paul, S. M. (1987) Steroid hormone metabolites potentiate GABA receptor-mediated chloride ion flux with nanomolar potency.Eur. J. Pharmacol. 142, 483–485.
Morrow, A. L., Suzdak, P. D. and Paul, S. M. (1988) Benzodiazepine, barbiturate, ethanol and hypnotic steroid hormone modulation of GABA-mediated chloride ion transport in rat brain synaptoneurosomes.Adv. Biochem. Psychopharmacol. 45, 247–261.
Moss S. J., Ravindran A., Mei L., Wang J. B., Kofuji P., Huganir R. L. and Burt D. R. (1991) Characterization of recombinant GABAA receptors produced in transfected cells from murine α1, β1, and γ2 subunit cDNAs.Neurosci. Lett. 123, 265–268.
Moss S. J., Smart T. G., Porter N. M., Nayeem N., Devine J., et al. (1990) Cloned GABA receptors are maintained in a stable cell line: allosteric and channel properties.Eur. J. Pharmacol. 189, 77–88.
Moss, S. J., Gorrie, G. H., Amato, A. and Smart, T. G. (1995) Modulation of GABAA receptors by tyrosine phosphorylation.Nature 377, 344–348.
Nagata K. and Narahashi T. (1994) Dual action of the cyclodiene insecticide dieldrin on the γ-aminobutyric acid receptor-chloride channel complex of rat dorsal root ganglion neurons.J. Pharmacol. Exp. Ther. 269, 164–171.
Nagata K., Hamilton B. J., Carter D. B. and Narahashi T. (1994) Selective effects of dieldrin on the GABAA receptor-channel subunits expressed in human embryonic kidney cells.Brain Res. 645, 19–26.
Nakahiro M., Yeh J. Z., Brunner E. and Narahashi T. (1989) General anesthetics modulate GABA receptor channel complex in rat dorsal root ganglion neurons.FASEB J. 3, 1850–1854.
Nayeem N., Green T. P., Martin I. L. and Barnard E. A. (1994) Quaternary structure of the native GABAA receptor determined by electron microscopic image analysis.J. Neurochem. 62, 815–818.
Nevo I. and Hamon M. (1995) Neurotransmitter and neuromodulatory mechanisms involved in alcohol abuse and alcoholism.Neurochem. Int. 26, 305–336.
Newland C. F. and Cull C. S. (1992) On the mechanism of action of picrotoxin on GABA receptor channels in dissociated sympathetic neurones of the rat.J. Physiol. Lond. 447, 191–213.
Nicoll R. A. (1978) The blockade of GABA mediated responses in the frog spinal cord by ammonium ions and furosemide.J. Physiol. Lond. 283, 121–132.
Nielsen M. and Braestrup C. (1980) Ethyl-β-carboline-3-carboxylate shows differential benzodiazepine receptor interaction.Nature 286, 606–607.
Nistri, A. and Sivilotti, L. (1985) An unusual effect of γ-aminobutyric acid on synaptic transmission of frog tectal neurones in vitro.Br. J. Pharmacol. 85, 917–921.
Nusser, Z., Sieghart, W., Stephenson, F. A. and Somogyi, P. (1996) The α6 subunit of the GABAA receptor is concentrated in both inhibitory and excitatory synapses on cerebellar granule cells.J. Neurosci. 16, 103–114.
Nutt D. J. (1990) Pharmacological mechanisms of benzodiazepine withdrawal.J. Psychiatr. Res. 2, 105–110.
Nutt D. J. (1990) The pharmacology of human anxiety.Pharmacol. Ther. 47, 233–266.
Nutt, D. J., Smith, C. F., Bennett, R. and Jackson, H. C. (1992) Investigations on the “set-point” theory of benzodiazepine receptor function.Adv. Biochem. Psychopharmacol. 47, 419–429.
Ogurusu T. and Shingai, R. (1996) Cloning of a putative γ-aminobutyric acid (GABA) receptor subunit rho 3 cDNA.Biochim. Biophys. Acta 1305, 15–18.
Olsen R. W. and Snowman A. M. (1982) Chloride-dependent enhancement by barbiturates of γ-aminobutyric acid receptor binding.J. Neurosci. 2, 1812–1823.
Olsen R. W. and Tobin A. J. (1990) Molecular biology of GABAA receptors.FASEB J. 4, 1469–1480.
Olsen R. W., Bergman, M. O., Van Ness, P. C., Lummis, S. C., Watkins A. E., Napias, C. and Greenlee, D. V. (1981) γ-Aminobutyric acid receptor binding in mammalian brain. Heterogeneity of binding sites.Mol. Pharmacol. 19, 217–227.
Olsen R. W., Yang J., King R. G., Dilber A., Stauber G. B. and Ransom R. W. (1986) Barbiturate and benzodiazepine modulation of GABA receptor binding and function.Life Sci. 39, 1969–1976.
Olsen, R. W. (1982) Drug interactions at the GABA receptor-ionophore complex.Annu. Rev. Pharmacol. Toxicol. 22, 245–277.
Olsen, R. W. and Snowman, A. M. (1983) [3H]bicuculline methochloride binding to low-affinity γ-aminobutyric acid receptor sites.J. Neurochem. 41, 1653–1663.
Ortells M. O. and Lunt G. G. (1995) Evolutionary history of the ligand-gated ion-channel super-family of receptors.Trends Neurosci. 18, 121–127.
Palmer M. R., van H. C., Harlan J. T. and Moore E. A. (1988) Antagonism of ethanol effects on cerebellar Purkinje neurons by the benzodiazepine inverse agonists Ro 15-4513 and FG 7142: electrophysiological studies.J. Pharmacol. Exp. Ther. 247, 1018–1024.
Pearce R. A. (1993) Physiological evidence for two distinct GABAA responses in rat hippocampus.Neuron 10, 189–200.
Peduto V. A., Concas A., Santoro G., Biggio G. and Gessa G. L. (1991) Biochemical and electrophysiologic evidence that propofol enhances GABAergic transmission in the rat brain.Anesthesiology 75, 1000–1009.
Peters, J. A., Kirkness, E. F., Callachan H., Lambert, J. J. and Turner, A. J. (1988) Modulation of the GABAA receptor by depressant barbiturates and pregnane steroids.Br. J. Pharmacol. 94, 1257–1269.
Petty F. (1995) GABA and mood disorders: a brief review and hypothesis.J. Affective Disord. 34, 275–281.
Polc, P. (1988) Electrophysiology of benzodiazepine receptor ligands: multiple mechanisms and sites of action.Prog. Neurobiol. 31, 349–423.
Polc, P., Bonetti, E. P., Schaffner, R. and Haefely, W. (1982) A three-state model of the benzodiazepine receptor explains the interactions between the benzodiazepine antagonist Ro 15-1788, benzodiazepine tranquilizers, β- carbolines, and phenobarbitone.Naunyn-Schmied. Arch. Pharmacol. 321, 260–264.
Pollard S., Duggan M. J. and Stephenson F. A. (1993) Further evidence for the existence of α subunit heterogeneity within discrete γ-aminobutyric acidA receptor subpopulations.J. Biol. Chem. 268, 3753–3757.
Pollard, S., Thompson, C. L. and Stephenson F. A. (1995) Quantitative characterization of α6 and α1 α6 subunit-containing native γ-aminobutyric acidA receptors of adult rat cerebellum demonstrates two α subunits per receptor oligomer.J. Biol. Chem. 270, 21,285–21,290.
Porter N. M., Angelotti T. P., Twyman R. E. and Macdonald R. L. (1992) Kinetic properties of α1β1 γ-aminobutyric acidA receptor channels expressed in Chinese hamster ovary cells: regulation by pentobarbital and picrotoxin.Mol. Pharmacol. 42, 872–881.
Poulter M. O., Barker J. L., O'Carroll A. M., Lolait S. J. and Mahan L. C. (1992) Differential and transient expression of GABAA receptor α-subunit mRNAs in the developing rat CNS.J. Neurosci. 12, 2888–2900.
Poulter M. O., Barker J. L., O'Carroll A. M., Lolait S. J. and Mahan L. C. (1993) Co-existent expression of GABAA receptor β2, β3 and γ2 subunit messenger RNAs during embryogenesis and early postnatal development of the rat central nervous system.Neuroscience 53, 1019–1033.
Pregenzer J. F., Im W. B., Carter D. B. and Thomsen D. R. (1993) Comparison of interactions of [3H]muscimol, t-butylbicyclophosphoro[35S]thionate, and [3H]flunitrazepam with cloned γ-aminobutyric acidA receptors of the α1β2 and α1β2γ2 subtypes.Mol. Pharmacol. 43, 801–806.
Prinz, H. and Striessnig, J. (1993) Ligand-induced accelerated dissociation of (+)-cis-diltiazem from L-type Ca2+ channels is simply explained by competition for individual attachment points.J. Biol. Chem. 268, 18,580–18,585.
Pritchett D. B. and Seeburg P. H. (1991) γ-Aminobutyric acid type A receptor point mutation increases the affinity of compounds for the benzodiazepine site.Proc. Natl. Acad. Sci. USA 88, 1421–1425.
Pritchett D. B., Lüddens H. and Seeburg P. H. (1989b) Type I and type II GABAA-benzodi-azepine receptors produced in transfected cells.Science 245, 1389–1392.
Pritchett D. B., Sontheimer H., Shivers B. D., Ymer S., Kettenmann H., Schofield P. R. and Seeburg P. H. (1989a) Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology.Nature 338, 582–585.
Pritchett, D. B. and Seeburg, P. H. (1990) γ-aminobutyric acidA receptor α5-subunit creates novel type II benzodiazepine receptor pharmacology.J. Neurochem. 54, 1802–1804.
Pritchett, D. B., Sontheimer, H., Gorman, C. M., Kettenmann, H., Seeburg, P. H. and Schofield P. R. (1988) Transient expression shows ligand gating and allosteric potentiation of GABAA receptor subunits.Science 242, 1306–1308.
Puia G., Ducic I., Vicini S. and Costa E. (1993) Does neurosteroid modulatory efficacy depend on GABAA receptor subunit composition?Rec. Channels 1, 135–142.
Puia G., Santi M. R., Vicini S., Pritchett D. B., Purdy R. H., et al. (1990) Neurosteroids act on recombinant human GABAA receptors.Neuron 4, 759–765.
Puia G., Santi M. R., Vicini S., Pritchett D. B., Seeburg P. H. and Costa E. (1989) Differences in the negative allosteric modulation of γ-aminobutyric acid receptors elicited by 4′-chlorodiazepam and by a β-carboline-3-carboxylate ester: a study with natural and reconstituted receptors.Proc. Natl. Acad. Sci. USA 86, 7275–7279.
Puia, G., Ducic, I., Vicini, S. and Costa, E. (1992) Molecular mechanisms of the partial allosteric modulatory effects of bretazenil at γ-aminobutyric acid type A receptor.Proc. Natl. Acad. Sci. USA 89, 3620–3624.
Puia, G., Vicini, S., Seeburg, P. H. and Costa, E. (1991) Influence of recombinant γ-aminobutyric acid-A receptor subunit composition on the action of allosteric modulators of γ-aminobutyric acidgated Cl-currents.Mol. Pharmacol. 39, 691–696.
Purdy R. H., Morrow A. L., Blinn J. R. and Paul S. M. (1990) Synthesis, metabolism and pharmacological activity of 3 alpha-hydroxy steroids which potentiate GABA-receptor-mediated chloride ion uptake in rat cerebral cortical synaptoneurosomes.J. Med. Chem. 33, 1572–1581.
Quirk K., Gillard N. P., Ragan C. I., Whiting P. J. and McKernan R. M. (1994) Model of subunit composition of γ-aminobutyric acidA receptor subtypes expressed in rat cerebellum with respect to their α and γ/δ subunits.J. Biol. Chem. 269, 16020–16028.
Quirk, K., Gillard, N. P., Ragan, C. I., Whiting, P. J. and McKernan, R. M. (1994) γ-Aminobutyric acid type a receptors in the rat brain can contain both γ2 and γ3 subunits, but γ1 does not exist in combination with another γ subunit.Mol. Pharmacol. 45, 1061–1070.
Rabow, L. E., Russek, S. J. and Farb, D. H. (1995) From ion currents to genomic analysis: recent advances in GABAA receptor research.Synapse 21, 189–274.
Ragan C. I., McKernan R. M., Wafford K. and Whiting P. J. (1993) γ-Aminobutyric acidA (GABAA) receptor/ion channel complex [published erratum appears inBiochem Soc. Trans. 1993 Nov;21(4):following 1201].Biochem. Soc. Trans. 21, 622–626.
Rastogi S. K. and Ticku M. K. (1985) A possible role of a GABAergic mechanism in the convulsant action of RO5-4864.Pharmacol. Biochem. Behav. 23, 285–288.
Rogers C. J., Twyman R. E. and Macdonald R. L. (1994) Benzodiazepine and β-carboline regulation of single GABAA receptor channels of mouse spinal neurones in culture.J. Physiol. Lond. 475, 69–82.
Rohrbough, J. and Spitzer, N. C. (1996) Regulation of intracellular Cl-levels by Na(+)-dependent Cl− cotransport distinguishes depolarizing from hyperpolarizing GABAA receptor-mediated responses in spinal neurons.J. Neurosci. 16, 82–91.
Rosenbaum J. F., Pollock R. A., Otto M. W. and Pollack M. H. (1995) Integrated treatment of panic disorder.Bull. Menninger. Clin. 59, A4–26.
Rupprecht, R., Berning, B., Hauser, C. A. E., Holsboer, F. and Reul, J. M. H. M. (1996) Steroid receptor-mediated effects of neuroactive steroids: Characterization of structure-activity relationship.Eur. J. Pharmacol. 303, 227–234.
Sakmann B., Hamill O. P. and Bormann J. (1983) Patch-clamp measurements of elementary chloride currents activated by the putative inhibitory transmitter GABA and glycine in mammalian spinal neurons.J. Neural. Transm. Suppl. 18, 83–95.
Sanna E. and Harris R. A. (1993) Recent developments in alcoholism: neuronal ion channels.Recent Dev. Alcohol. 11, 169–186.
Sanna E., Garau F. and Harris R. A. (1995) Novel properties of homomeric β1 γ-aminobutyric acid type A receptors: actions of the anesthetics propofol and pentobarbital.Mol. Pharmacol. 47, 213–217.
Saxena N. C. and Macdonald R. L. (1994) Assembly of GABAA receptor subunits—role of the δ-subunit.J. Neurosci. 14, 7077–7086.
Saxena N. C. and Macdonald R. L. (1996) Properties of putative cerebellar γ-aminobutyric acidA receptor isoforms.Mol. Pharmacol. 49, 567–579.
Schlatter E., Greger R. and Weidtke C. (1983) Effect of “high ceiling” diuretics on active salt transport in the cortical thick ascending limb of Henle's loop of rabbit kidney. Correlation of chemical structure and inhibitory potency.Pflügers. Arch. 396, 210–217.
Schofield P. R., Darlison M. G., Fujita N., Burt D. R., Stephenson F. A. et al. (1987) Sequence and functional expression of the GABAA receptor shows a ligand-gated receptor super-family.Nature 328, 221–227.
Seeburg P. H., Wisden W., Verdoorn T. A., Pritchett D. B., Werner P. et al. (1990) The GABAA receptor family—molecular and functional diversity.Cold Spring Harbor Symp. Quantit. Biol. 55, 29–40.
Sequier J. M., Richards J. G., Malherbe P., Price G. W., Mathews S. and Möhler H. (1988) Mapping of brain areas containing RNA homologous to cDNAs encoding the α and β subunits of the rat GABAA γ-aminobutyrate receptor.Proc. Natl. Acad. Sci. USA 85, 7815–7819.
Serafini R., Valeyev, A. Y., Barker, J. L. and Poulter, M. O. (1995) Depolarizing GABA-activated Cl− channels in embryonic rat spinal and olfactory bulb cells.J. Physiol. Lond. 488, 371–386.
Shimada S., Cutting G. and Uhl G. R. (1992) γ-Aminobutyric acidA or C receptor? γ- Aminobutyric acid α1 receptor RNA induces bicuculline-, barbiturate-, and benzodiazepine-insensitive γ-aminobutyric acid responses inXenopus oocytes.Mol. Pharmacol. 41, 683–687.
Shingai R., Sutherland M. L. and Barnard E. A. (1991) Effects of subunit types of the cloned GABAA receptor on the response to a neurosteroid.Eur. J. Pharmacol. 206, 77–80.
Shivers B. D., Killisch I., Sprengel R., Sontheimer H., Köhler M., Schofield P. R. and Seeburg P. H. (1989) Two novel GABAA receptor subunits exist in distinct neuronal subpopulations.Neuron 3, 327–337.
Sieghart W. (1983) Several new benzodiazepines selectively interact with a benzodiazepine receptor subtype.Neurosci. Lett. 38, 73–78.
Sieghart W. (1994) Pharmacology of benzodiazepine receptors: an update.J. Psychiatry Neurosci. 19, 24–29.
Sieghart W. (1995) Structure and pharmacology of γ-aminobutyric acidA receptor subtypes.Pharmacol. Rev. 47, 181–234.
Sigel E. and Barnard F. A. (1984) A γ-aminobutyric acid/benzodiazepine receptor complex from bovine cerebral cortex. Improved purification with preservation of regulatory sites and their interactions.J. Biol. Chem. 259, 7219–7223.
Sigel E., Baur R. and Malherbe P. (1993) Recombinant GABAA receptor function and ethanol.FEBS Lett. 324, 140–142.
Sigel E., Baur R., Kellenberger S. and Malherbe P. (1992) Point mutations affecting antagonist affinity and agonist dependent gating of GABAA receptor channels.EMBO J. 11, 2017–2023.
Sigel E., Baur R., Malherbe P. and Möhler H. (1989) The rat β1-subunit of the GABAA receptor forms a picrotoxin-sensitive anion channel open in the absence of GABA.FEBS Lett. 257, 377–379.
Sigel E., Baur R., Trube G., Möhler H. and Malherbe P. (1990) the effect of subunit composition of rat brain GABAA receptors on channel function.Neuron 5, 703–711.
Sigel E., Stephenson F. A., Mamalaki C. and Barnard E. A. (1983) A γ-aminobutyric acid/benzodiazodiazepine receptor complex of bovine cerebral cortex.J. Biol. Chem. 258, 6965–6971.
Sigel, E. and Kannenberg, K. (1996) GABAA receptor subtypes.Trends Neurosci. 19, 386.
Sivilotti L. and Nistri A. (1991) GABA receptor mechanisms in the central nervous system.Prog. Neurobiol. 36, 35–92.
Sivilotti, L. and Nistri, A. (1989) Pharmacology of a novel effect of γ-aminobutyric acid on the frog optic tectum in vitro.Eur. J. Pharmacol. 164, 205–212.
Skerritt J. H. and Johnston G. A. (1983) Interactions of some anaesthetic, convulsant, and anticonvulsant drugs at GABA-benzodiazepine receptorionophore complexes in rat brain synaptosomal membranes.Neurochem. Res. 8, 1351–1362.
Skolnick P., Trullas R., Havoundjian H. and Paul S. (1986) The benzodiazepine/GABA receptor complex in anxiety.Clin. Neuropharmacol. 4, 43–45.
Slany A., Zezula J., Fuchs K. and Sieghart W. (1995) Allosteric modulation of [3H]flunitrazepam binding to recombinant GABAA receptors.Eur. J. Pharmacol-Molec. Pharm. 291, 99–105.
Slany A., Zezula J., Tretter V. and Sieghart W. (1995) Rat β 3 subunits expressed in human embryonic kidney 293 cells form high affinity [35S]t-butylbicyclophosphorothionate binding sites modulated by several allosteric ligands of γ-aminobutyric acid type a receptors.Mol. Pharmacol. 48, 385–391.
Smart T. G. and Constanti A. (1990) Differential effect of zinc on the vertebrate GABAA-receptor complex.Br. J. Pharmacol. 99, 643–654.
Smith G. B. and Olsen R. W. (1994) Identification of a [3H]muscimol photoaffinity substrate in the bovine γ-aminobutyric acidA receptor α subunit.J. Biol. Chem. 269, 20,380–20,387.
Smith G. B. and Olsen R. W. (1995) Functional domains of GABAA receptors.Trends Pharmacol. Sci. 16, 162–168.
Squires R. F. and Saederup E. (1987) GABAA receptor blockers reverse the inhibitory effect of GABA on brain-specific [35S]TBPS binding.Brain Res. 414, 357–364.
Squires R. F., Benson D. I., Braestrup C., Coupet J., Klepner C. A., Myers V. and Beer B. (1979) Some properties of brain specific benzodiazepine receptors: new evidence for multiple receptors.Pharmacol. Biochem. Behav. 10, 825–830.
Squires R. F., Casida J. E., Richardson M. and Saederup E. (1983) [35S]t-butylbicyclophosphorothionate binds with high affinity to brain-specific sites coupled to γ-aminobutyric acidA and ion recognition sites.Mol. Pharmacol. 23, 326–336.
Staley K. J., Soldo B. L. and Proctor, W. R. (1995) Ionic mechanisms of neuronal excitation by inhibitory GABAA receptors.Science 269, 977–981.
Staley K., Smith R., Schaack, J., Wilcox, C. and Jentsch, T. J. (1996) Alteration of GABAA receptor function following gene transfer of the CLC-2 chloride channel.Neuron 17, 543–551.
Stevenson A., Wingrove P. B., Whiting P. J. and Wafford K. A. (1995) β-Carboline γ-aminobutyric acidA receptor inverse agonists modulate γ-aminobutyric acid via the loreclezole binding site as well as the benzodiazepine site.Mol. Pharmacol. 48, 965–969.
Strata F. and Cherubini, E. (1994) Transient expression of a novel type of GABA response in rat CA3 hippocampal neurones during development.J. Physiol. Lond. 480, 493–503.
Study, R. E. and Barker, J. L. (1981) Diazepam and pentobarbital: fluctuation analysis reveals different mechanisms for potentiation of γ-aminobutyric acid responses in cultured central neurons.Proc. Natl. Acad. Sci. USA 78, 7180–7184.
Supavilai P. and Karobath M. (1983) Differential modulation of [35S]TBPS binding by the occupancy of benzodiazepine receptors with its ligands.Eur. J. Pharmacol. 91, 145–146.
Suzdak P. D., Glowa J. R., Crawley J. N., Schwartz R., Skolnick P. and Paul S. M. (1986) A Selective Imidazobenzodiazepine Antagonist of Ethanol in the Rat.Science 234, 1243–1247.
Suzdak P. D., Paul S. M. and Crawley J. N. (1988) Effects of Ro15-4513 and other benzodiazepine receptor inverse agonists on alcohol-induced intoxication in the rat.J. Pharmacol. Exp. Ther. 245, 880–886.
Tabakoff B. and Hoffman P. L. (1996) Alcohol addiction: an enigma among us.Neuron 16, 909–912.
Taguchi J. and Kuriyama K. (1990) Functional modulation of cerebral γ-aminobutyric acidA receptor/benzodiazepine receptor/chloride ion channel complex with ethyl β-carboline-3-carboxylate: presence of independent binding site for ethyl β-carboline-3-carboxylate.J. Pharmacol. Exp. Ther. 253, 558–566.
Taleb O., Trouslard J., Demeneix B. A., Feltz P., Bossu J. L., Dupont J. L. and Feltz A. (1987) Spontaneous and GABA-evoked chloride channels on pituitary intermediate lobe cells and their internal Ca requirements.Pflugers. Arch. 409, 620–631.
Tallman J. F., Thomas J. W. and Gallager, D. W. (1978) GABAergic modulation of benzodiazepine binding site sensitivity.Nature 288, 609–610.
Thomas, J. W. and Tallman, J. F. (1983) Photoaffinity labeling of benzodiazepine receptors causes altered agonist- antagonist interactions.J. Neurosci. 3, 433–440.
Thompson S. M. and Gahwiler B. H. (1989) Activity-dependent disinhibition. II. Effects of extracellular potassium, furosemide, and membrane potential on ECI-in hippocampal CA3 neurons.J. Neurophysiol. 61, 512–523.
Thompson S. M., Deisz R. A. and Prince D. A. (1988) Relative contributions of passive equilibrium and active transport to the distribution of chloride in mammalian cortical neurons.J. Neurophysiol. 60, 105–124.
Ticku M. K. and Olsen R. W. (1978) Interaction of barbiturates with dihydropicrotoxinin binding sites related to the GABA receptor-ionophore system.Life Sci. 22, 1643–1651.
Tierney M. L., Birnir B., Pillai N. P., Clements J. D., Howitt S. M., Cox G. B. and Gage P. W. (1996) Effects of mutating leucine to threonine in the M2 segment of α1 and β1 subunits of GABAA α1 β1 receptors.J. Mem. Biol. 154, 11–21.
Tretter, V., Ehya, N., Fuchs, K. and Sieghart, W. (1997) Stoichiometry and assembly of a recombinant GABAA receptor subtype.J. Neurosci. 17, 2728–2737.
Trifiletti, R. R. and Snyder, S. H. (1984) Anxiolytic cyclopyrrolones zopiclone and suriclone bind to a novel site linked allosterically to benzodiazepine receptors.Mol. Pharmacol. 26, 458–469.
Trifiletti, R. R., Snowman, A. M. and Snyder, S. H. (1984) Anxiolytic cyclopyrrolone drugs allosterically modulate the binding of [35S]t-butylbicyclophosphorothionate to the benzodiazepine/γ-aminobutyric acid-A receptor/chloride anionophore complex.Mol. Pharmacol. 26, 470–476.
Tsoi W. F. (1991) Insomnia: drug treatment.Ann. Acad. Med. Singapore 20, 269–272.
Turner, D. M., Ransom, R. W., Yang, J. S. and Olsen, R. W. (1989) Steroid anesthetics and naturally occurring analogs modulate the γ-aminobutyric acid receptor complex at a site distinct from barbiturates.J. Pharmacol. Exp. Ther. 248, 960–966.
Twyman R. E. and Macdonald R. L. (1992) Neurosteroid regulation of GABAA receptor single-channel kinetic properties of mouse spinal cord neurons in culture.J. Physiol. Lond. 456, 215–245.
Twyman R. E., Rogers C. J. and Macdonald R. L. (1989a) Pentobarbital and picrotoxin have recip-rocal actions on single GABAA receptor channels.Neurosci. Lett. 96, 89–95.
Twyman R. E., Rogers C. J. and Macdonald R. L. (1989b) Differential regulation of γ-aminobutyric acid receptor channels by diazepam and phenobarbital.Ann. Neurol. 25, 213–220.
Twyman R. E., Rogers C. J. and Macdonald R. L. (1990) Intraburst kinetic properties of the GABAA receptor main conductance state of mouse spinal cord neurones in culture.J. Physiol. Lond. 423, 193–220.
Twyman R. E., Green R. M. and Macdonald, R. L. (1992) Kinetics of open channel block by penicillin of single GABAA receptor channels from mouse spinal cord neurones in culture.J. Physiol. Lond. 445, 97–127.
Unwin N. (1989) The structure of ion channels in membranes of excitable cells.Neuron 3, 665–676.
Unwin N. (1993) Nicotinic acetylcholine receptor at 9 A resolution.J. Mol. Biol. 229, 1101–1124.
Unwin N. (1995) Acetylcholine receptor channel imaged in the open state.Nature 373, 37–43.
Uusi Oukari M. and Korpi E. R. (1989) Cerebellar GABAA receptor binding and function in vitro in two rat lines developed for high and low alcohol sensitivity.Neurochem. Res. 14, 733–739.
Van Renterghem C., Bilbe G., Moss S., Smart T. G., Constanti A., Brown D. A. and Barnard E. A. (1987) GABA receptors induced in Xenopus oocytes by chick brain mRNA: evaluation of TBPS as a use-dependent channel-blocker.Brain Res. 388, 21–31.
Varecka, L., Wu C. H., Rotter A. and Frostholm, A. (1994) GABAA/benzodiazepine receptor α6 subunit mRNA granule cells of the cerebellar cortex and cochlear nuclei: expression in developing and mutant mice.J. Comp. Neurol. 339, 341–352.
Verdoorn T. A. (1994) Formation of heteromeric γ-aminobutyric acid type A receptors containing two different α subunits.Mol. Pharmacol. 45, 475–480.
Verdoorn T. A., Draguhn A., Ymer S., Seeburg P. H. and Sakmann B. (1990) Functional properties of recombinant rat GABAA receptors depend upon subunit composition.Neuron 4, 919–928.
von Blankenfeld G., Ymer S., Pritchett D. B., Sontheimer H., Ewert M., Seeburg P. H. and Kettenmann H. (1990) Differential benzodiazepine pharmacology of mammalian recombinant GABAA receptors.Neurosci. Lett. 115, 269–273.
von Blankenfeld, G. and Kettenmann H. (1991) Glutamate and GABA receptors in vertebrate glial cells.Mol. Neurobiol. 5, 31–43.
Wafford K. A. and Whiting P. J. (1992) Ethanol potentiation of GABAA receptors requires phosphorylation of the alternatively spliced variant of the γ2 subunit.FEBS Lett. 313, 113–117.
Wafford K. A., Bain C. J., Quirk K., Mckernan R. M., Wingrove P. B., Whiting P. J. and Kemp J. A. (1994) A novel allosteric modulatory site on the GABAA receptor β subunit.Neuron 12, 775–782.
Wafford, K. A., Whiting, P. J. and Kemp, J. A. (1993a) Differences in affinity and efficacy of benzodiazepine receptor ligands at recombinant γ-aminobutyric acidA receptor subtypes.Mol. Pharmacol. 43, 240–244.
Wafford K. A., Bain C. J., Whiting P. J. and Kemp J. A. (1993b) Functional comparison of the role of γ subunits in recombinant human γ-aminobutyric acidA/benzodiazepine receptors.Mol. Pharmacol. 44, 437–442.
Wafford, K. A., Burnett, D. M., Leidenheimer, N. J., Burt, D. R., Wang, J. B., et al. (1991) Ethanol sensitivity of the GABAA receptor expressed inXenopus oocytes requires 8 amino acids contained in the γ2L subunit.Neuron 7, 27–33.
Wakamori M., Ikemoto Y. and Akaike N. (1991) Effects of two volatile anesthetics and a volatile convulsant on the excitatory and inhibitory amino acid responses in dissociated CNS neurons of the rat.J. Neurophysiol. 66, 2014–2021.
Weissman B. A., Cott J., Hommer D., Quirion R., Paul S. and Skolnick P. (1983) Pharmacological, electrophysiological, and neurochemical actions of the convulsant benzodiazepine Ro 5-4864 (4′-chlordiazepam).Adv. Biochem. Psychopharmacol. 38, 139–151.
White G. and Gurley D. A. (1995) α subunits influence Zn block of γ 2 containing GABAA receptor currents.Neuroreport 6, 461–464.
White, G. (1992) Heterogeneity in EC50 and nM of GABAA receptors on dorsal root ganglion neurons freshly isolated from adult rats.Brain Res. 585, 56–62.
Whiting P., McKernan R. M. and Iversen, L. L. (1990) Another mechanism for creating diversity in γ-aminobutyrate type A receptors: RNA splicing directs expression of two forms of γ2 phosphorylation site.Proc. Natl. Acad. Sci. USA 87, 9966–9970.
Wieland H. A. and Lüddens H. (1994) Four amino acid exchanges convert a diazepam-insensitive, inverse agonist-preferring GABAA receptor into a diazepam-preferring GABAA receptor.J. Med. Chem. 37, 4576–4580.
Wieland H., Lüddens H. and Seeburg P. H. (1992) A single histidine in GABAA receptors is essential for benzodiazepine agonist binding.J. Biol. Chem. 257, 1426–1429.
Wilke K., Gaul R. and Poustka A. (1997) Complex alternative splicing as a mechanism for tissue specific expression of a gene defining the putative new subunit class ε of the GABAA neurotransmitter receptor (submitted).
Williamson, R. E. and Pritchett, D. B. (1994) Levels of benzodiazepine receptor subtypes and GABAA receptor α-subunit mRNA do not correlate during development.J. Neurochem. 63, 413–418.
Wingrove P. B., Wafford K. A., Bain C. and Whiting P. J. (1994) The modulatory action of loreclezole at the γ-aminobutyric acid type A receptor is determined by a single amino acid in the β2 and β3 subunit.Proc. Natl. Acad. Sci. USA 91, 4569–4573.
Wisden W., Herb A., Wieland H., Keinanen K., Lüddens H. and Seeburg P. H. (1991) Cloning, pharmacological characteristics and expression pattern of the rat GABAA receptor α 4 subunit.FEBS Lett. 289, 227–230.
Wisden W., Laurie D. J., Monyer H. and Seeburg P. H. (1992) The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, Diencephalon, Mesencephalon.J. Neurosci. 12, 1040–1062.
Wisden W., Gundlach A. L., Barnard E. A., Seeburg, P. H. and Hunt S. P. (1991) Distribution of GABAA receptor subunit mRNAs in rat lumbar spinal cord.Brain Res. Mol. Brain Res. 10, 179–183.
Wong D. T., Threlkeld P. G., Bymaster F. P. and Squires R. F. (1984) Saturable binding of35S-t-butylbicyclophosphorothionate to the sites linked to the GABA receptor and the interaction with GABAergic agents.Life Sci. 34, 853–860.
Wong G. and Skolnick P. (1992) High affinity ligands for ‘diazepam-insensitive’ benzodiazepine receptors.Eur. J. Pharmacol. 225, 63–68.
Wong G., Sei Y. and Skolnick P. (1992) Stable expression of type I γ-aminobutyric acidA/benzodiazepine receptors in a transfected cell line.Mol. Pharmacol. 42, 996–1003.
Xu M. and Akabas M. H. (1996) Identification of channel-lining residues in the M2 membrane-spanning segment of the GABAA receptor α1 subunit.J. Gen. Physiol. 107, 195–205.
Xu M., Covey D. F. and Akabas M. H. (1995) Interaction of picrotoxin with GABAA receptor channel-lining residues probed in cysteine mutants.Biophys. J. 69, 1858–1867.
Yakushiji T., Fukuda T., Oyama Y. and Akaike N. (1989) Effects of benzodiazepines and non-benzodiazepine compounds on the GABA-induced response in frog isolated sensory neurones.Br. J. Pharmacol. 98, 735–740.
Yakushiji T., Tokutomi N. and Akaike N. (1989) Augmentation of GABA-induced chloride current in frog sensory neurons by diazepam.Neurosci. Res. 6, 309–320.
Yang J., Isenberg K. E. and Zorumski C. F. (1992) Volatile anesthetics gate a chloride current in postnatal rat hippocampal neurons.FASEB J. 6, 914–918.
Yang J. S. and Olsen R. W. (1987) γ-Aminobutyric acid receptor-regulated36Cl-flux in mouse cortical slices.J. Pharmacol. Exp. Ther. 241, 677–685.
Ymer S., Draguhn A., Wisden W., Werner P., Keinänen K. et al. (1990) Structural and functional characterization of the γ1 subunit of GABAA/benzodiazepine receptors.EMBO J. 9, 3261–3267.
Ymer S., Schofield P. R., Draguhn A., Werner P., Köhler M. and Seeburg P. H. (1989) GABAA receptor β subunit heterogeneity: functional expression of cloned cDNAs.EMBO J. 8, 1665–1670.
Yoon K. W., Covey D. F. and Rothman S. M. (1993) Multiple mechanisms of picrotoxin block of GABA-induced currents in rat hippocampal neurons.J. Physiol. Lond. 464, 423–439.
Zaman S. H., Shingai R., Harvey R. J., Darlison M. G. and Barnard E. A. (1992) Effects of subunit types of the recombinant GABAA receptor on the response to a neurosteroid.Eur. J. Pharmacol. 225, 321–330.
Zdilar D., Luntz Leybman V., Frostholm A. and Rotter A. (1992) Differential expression of GABAA/benzodiazepine receptor β1, β2, and β3 subunit mRNAs in the developing mouse cerebellum.J. Comp. Neurol. 326, 580–594.
Zezula J., Slany A. and Sieghart W. (1996) Interaction of allosteric ligands with GABAA receptors containing one, two, or three different subunits.Eur. J. Pharmacol. 301, 207–214.
Zhang L., Spigelman I. and Carlen P. L. (1991) Development of GABA-mediated, chloride-dependent inhibition in CA1 pyramidal neurones of immature rat hippocampal slices.J. Physiol. Lond. 444, 25–49.
Zhang, J. H., Sato, M. and Tohyama, M. (1991) Region-specific expression of the mRNAs encoding β subunits (β1, β2, and β3) of GABAA receptor in the rat brain.J. Comp. Neurol. 303, 637–657.
Zhu W. J., Wang J. F., Krueger K. E. and Vicini S. (1996) δ subunit inhibits neurosteroid modulation of GABAA receptors.J. Neurosci. 16, 6648–6656.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hevers, W., Lüddens, H. The diversity of GABAA receptors. Mol Neurobiol 18, 35–86 (1998). https://doi.org/10.1007/BF02741459
Issue Date:
DOI: https://doi.org/10.1007/BF02741459