{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T14:24:29Z","timestamp":1775917469856,"version":"3.50.1"},"reference-count":0,"publisher":"University of Edinburgh","issue":"3","license":[{"start":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T00:00:00Z","timestamp":1630540800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-sa\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["GtoPdb CITE"],"abstract":"<jats:p>The GABAA receptor is a ligand-gated ion channel of the Cys-loop family that includes the nicotinic acetylcholine, 5-HT3 and strychnine-sensitive glycine receptors. GABAA receptor-mediated inhibition within the CNS occurs by fast synaptic transmission, sustained tonic inhibition and temporally intermediate events that have been termed 'GABAA, slow' [45]. GABAA receptors exist as pentamers of 4TM subunits that form an intrinsic anion selective channel. Sequences of six \u03b1, three \u03b2, three \u03b3, one \u03b4, three \u03c1, one \u03b5, one \u03c0 and one \u03b8 GABAA receptor subunits have been reported in mammals [278, 235, 236, 283]. The \u03c0-subunit is restricted to reproductive tissue. Alternatively spliced versions of many subunits exist (e.g. \u03b14- and \u03b16- (both not functional) \u03b15-, \u03b22-, \u03b23- and \u03b32), along with RNA editing of the \u03b13 subunit [71]. The three \u03c1-subunits, (\u03c11-3) function as either homo- or hetero-oligomeric assemblies [359, 50]. Receptors formed from \u03c1-subunits, because of their distinctive pharmacology that includes insensitivity to bicuculline, benzodiazepines and barbiturates, have sometimes been termed GABAC receptors [359], but they are classified as GABAA receptors by NC-IUPHAR on the basis of structural and functional criteria [16, 235, 236].Many GABAA receptor subtypes contain \u03b1-, \u03b2- and \u03b3-subunits with the likely stoichiometry 2\u03b1.2\u03b2.1\u03b3 [168, 235]. It is thought that the majority of GABAA receptors harbour a single type of \u03b1- and \u03b2 -subunit variant. The \u03b11\u03b22\u03b32 hetero-oligomer constitutes the largest population of GABAA receptors in the CNS, followed by the \u03b12\u03b23\u03b32 and \u03b13\u03b23\u03b32 isoforms. Receptors that incorporate the \u03b14- \u03b15-or \u03b16-subunit, or the \u03b21-, \u03b31-, \u03b33-, \u03b4-, \u03b5- and \u03b8-subunits, are less numerous, but they may nonetheless serve important functions. For example, extrasynaptically located receptors that contain \u03b16- and \u03b4-subunits in cerebellar granule cells, or an \u03b14- and \u03b4-subunit in dentate gyrus granule cells and thalamic neurones, mediate a tonic current that is important for neuronal excitability in response to ambient concentrations of GABA [209, 272, 83, 19, 288]. GABA binding occurs at the \u03b2+\/\u03b1- subunit interface and the homologous \u03b3+\/\u03b1- subunits interface creates the benzodiazepine site. A second site for benzodiazepine binding has recently been postulated to occur at the \u03b1+\/\u03b2- interface ([254]; reviewed by [282]). The particular \u03b1-and \u03b3-subunit isoforms exhibit marked effects on recognition and\/or efficacy at the benzodiazepine site. Thus, receptors incorporating either \u03b14- or \u03b16-subunits are not recognised by \u2018classical\u2019 benzodiazepines, such as flunitrazepam (but see [356]). The trafficking, cell surface expression, internalisation and function of GABAA receptors and their subunits are discussed in detail in several recent reviews [52, 140, 188, 316] but one point worthy of note is that receptors incorporating the \u03b32 subunit (except when associated with \u03b15) cluster at the postsynaptic membrane (but may distribute dynamically between synaptic and extrasynaptic locations), whereas as those incorporating the \u03b4 subunit appear to be exclusively extrasynaptic. NC-IUPHAR [16, 235, 3, 2] class the GABAA receptors according to their subunit structure, pharmacology and receptor function. Currently, eleven native GABAA receptors are classed as conclusively identified (i.e., \u03b11\u03b22\u03b32, \u03b11\u03b2\u03b32, \u03b13\u03b2\u03b32, \u03b14\u03b2\u03b32, \u03b14\u03b22\u03b4, \u03b14\u03b23\u03b4, \u03b15\u03b2\u03b32, \u03b16\u03b2\u03b32, \u03b16\u03b22\u03b4, \u03b16\u03b23\u03b4 and \u03c1) with further receptor isoforms occurring with high probability, or only tentatively [235, 236]. It is beyond the scope of this Guide to discuss the pharmacology of individual GABAA receptor isoforms in detail; such information can be gleaned in the reviews [16, 95, 168, 173, 143, 278, 216, 235, 236] and [9, 10]. Agents that discriminate between \u03b1-subunit isoforms are noted in the table and additional agents that demonstrate selectivity between receptor isoforms, for example via \u03b2-subunit selectivity, are indicated in the text below. The distinctive agonist and antagonist pharmacology of \u03c1 receptors is summarised in the table and additional aspects are reviewed in [359, 50, 145, 223].Several high-resolution cryo-electron microscopy structures have been described in which the full-length human \u03b11\u03b23\u03b32L GABAA receptor in lipid nanodiscs is bound to the channel-blocker picrotoxin, the competitive antagonist bicuculline, the agonist GABA (\u03b3-aminobutyric acid), and the classical benzodiazepines alprazolam and diazepam [198].<\/jats:p>","DOI":"10.2218\/gtopdb\/f72\/2021.3","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T09:30:22Z","timestamp":1632907822000},"source":"Crossref","is-referenced-by-count":7,"title":["GABA&lt;sub&gt;A&lt;\/sub&gt; receptors in GtoPdb v.2021.3"],"prefix":"10.2218","volume":"2021","author":[{"given":"Delia","family":"Belelli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim G.","family":"Hales","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy J.","family":"Lambert","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernhard","family":"Luscher","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Olsen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4277-4245","authenticated-orcid":false,"given":"John A.","family":"Peters","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9396-4746","authenticated-orcid":false,"given":"Uwe","family":"Rudolph","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0443-0302","authenticated-orcid":false,"given":"Werner","family":"Sieghart","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"5235","published-online":{"date-parts":[[2021,9,2]]},"container-title":["IUPHAR\/BPS Guide to Pharmacology CITE"],"original-title":[],"link":[{"URL":"http:\/\/journals.ed.ac.uk\/gtopdb-cite\/article\/download\/6411\/8637","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.ed.ac.uk\/gtopdb-cite\/article\/download\/6411\/8638","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.ed.ac.uk\/gtopdb-cite\/article\/download\/6411\/8636","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.ed.ac.uk\/gtopdb-cite\/article\/download\/6411\/8637","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T09:31:02Z","timestamp":1632907862000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.ed.ac.uk\/gtopdb-cite\/article\/view\/6411"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,2]]},"references-count":0,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,9,2]]}},"URL":"https:\/\/doi.org\/10.2218\/gtopdb\/f72\/2021.3","relation":{},"ISSN":["2633-1020"],"issn-type":[{"value":"2633-1020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,2]]}}}