Gamma-aminobutyric acid type A receptor alpha-5 beta-3 gamma-2 (α5β3γ2 GABA_A receptor) (α5β3γ2 GABA_A receptor)

The Gamma-aminobutyric acid type A receptor alpha-5 beta-3 gamma-2 (α5β3γ2 GABA_A receptor) is a pentameric ligand-gated ion channel that mediates inhibitory neurotransmission in the central nervous system (Source: UniProt P31644). This specific receptor subtype is primarily localized in the hippocampus and cerebral cortex, where it is found predominantly at extrasynaptic sites (Source: PubMed PMID: 22438296). Unlike synaptic GABA_A receptors that mediate phasic inhibition, the α5-containing receptors generate a persistent tonic inhibitory current that regulates neuronal excitability and synaptic plasticity (Source: PubMed PMID: 24930902). Due to its role in modulating cognitive processes, the α5β3γ2 receptor is a significant therapeutic target for conditions involving cognitive deficit, such as Down syndrome, Alzheimer's disease, and schizophrenia (Source: ClinicalTrials.gov NCT02024789). Pharmacological strategies often involve negative allosteric modulators (NAMs) to enhance memory and learning by reducing tonic inhibition, or positive allosteric modulators (PAMs) for potential antidepressant effects (Source: PubMed PMID: 28807937). A major challenge in targeting this receptor is achieving high subtype selectivity to avoid the sedative and ataxic side effects associated with broader GABA_A receptor activation (Source: StatPearls, GABA Receptor Modulators).

Other names

GABRA5-GABRB3-GABRG2 receptorAlpha-5 containing GABA-A receptorα5-GABAARGABA(A) receptor alpha5beta3gamma2

Modulation of chloride ion conductance through the receptor pore via allosteric binding at the benzodiazepine site (alpha/gamma interface) or the GABA binding site (alpha/beta interface).