GABA<sub>A</sub> receptors in GtoPdb v.2023.1

The GABAA receptor is a ligand-gated ion channel of the Cys-loop family that includes nicotinic acetylcholine, 5-HT3 and strychnine-sensitive glycine receptors. receptor-mediated inhibition within CNS occurs by fast synaptic transmission, sustained tonic temporally intermediate events have been termed 'GABAA, slow' [45]. receptors exist as pentamers 4TM subunits form an intrinsic anion selective channel. Sequences six α, three β, γ, one δ, ρ, ε, π θ reported in mammals [281, 237, 238, 288]. π-subunit restricted to reproductive tissue. Alternatively spliced versions many (e.g. α4- α6- (both not functional) α5-, β2-, β3- γ2), along with RNA editing α3 subunit [71]. ρ-subunits, (ρ1-3) function either homo- or hetero-oligomeric assemblies [365, 50]. Receptors formed from because their distinctive pharmacology insensitivity bicuculline, benzodiazepines barbiturates, sometimes GABAC [365], but they are classified NC-IUPHAR on basis structural functional criteria [16, 238].Many subtypes contain α-, β- γ-subunits likely stoichiometry 2α.2β.1γ [170, 237]. It thought majority harbour single type α- β -subunit variant. α1β2γ2 hetero-oligomer constitutes largest population CNS, followed α2β3γ2 α3β3γ2 isoforms. incorporate α5-or α6-subunit, β1-, γ1-, γ3-, δ-, ε- θ-subunits, less numerous, may nonetheless serve important functions. For example, extrasynaptically located δ-subunits cerebellar granule cells, δ-subunit dentate gyrus cells thalamic neurones, mediate current for neuronal excitability response ambient concentrations GABA [211, 275, 84, 19, 293]. binding at β+/α- interface homologous γ+/α- creates benzodiazepine site. A second site has recently postulated occur α+/β- ([257]; reviewed [287]). particular α-and γ-subunit isoforms exhibit marked effects recognition and/or efficacy Thus, incorporating α6-subunits recognised ‘classical’ benzodiazepines, such flunitrazepam (but see [362]). trafficking, cell surface expression, internalisation discussed detail several recent reviews [52, 141, 190, 322] point worthy note γ2 (except when associated α5) cluster postsynaptic membrane distribute dynamically between extrasynaptic locations), whereas those δ appear be exclusively extrasynaptic. 3, 2] class according structure, function. Currently, eleven native classed conclusively identified (i.e., α1β2γ2, α2βγ2, α3βγ2, α4βγ2, α4β2δ, α4β3δ, α5βγ2, α6βγ2, α6β2δ, α6β3δ ρ) further occurring high probability, only tentatively [237, 238]. beyond scope this Guide discuss individual detail; information can gleaned 96, 170, 175, 144, 281, 218, 284, 9, 10]. Agents discriminate α-subunit noted table additional agents demonstrate selectivity isoforms, example via β-subunit selectivity, indicated text below. agonist antagonist ρ summarised aspects 50, 146, 225].Several high-resolution cryo-electron microscopy structures described which full-length human α1β3γ2L lipid nanodiscs bound channel-blocker picrotoxin, competitive (γ-aminobutyric acid), classical alprazolam diazepam [200].