Gamma-aminobutyric acid type A receptor (alpha1, alpha2, alpha3, or alpha5 and gamma2 subunit-containing) (GABA_A receptor (alpha1/2/3/5-gamma2))

The gamma-aminobutyric acid type A (GABA_A) receptor is a pentameric ligand-gated chloride channel that serves as the primary mediator of rapid inhibitory neurotransmission in the mammalian central nervous system (Olsen & Sieghart, 2008, PMID: 18652635). Receptors composed of alpha1, alpha2, alpha3, or alpha5 subunits in complex with a gamma2 subunit are uniquely defined by their sensitivity to benzodiazepines, which bind to a specific allosteric site at the alpha-gamma2 interface (Sigel & Steinmann, 2012, PMID: 22300836). The physiological outcome of receptor activation depends on the specific alpha subunit: alpha1 mediates sedation and anticonvulsant activity, alpha2 and alpha3 are primarily responsible for anxiolytic and muscle-relaxant effects, and alpha5 is associated with cognitive processes (Rudolph & Knoflach, 2011, PMID: 21552287). These receptors are critical therapeutic targets for treating anxiety, insomnia, and epilepsy, as their modulation directly alters neuronal firing rates (Atack, 2011, PMID: 21112002). However, non-selective activation often leads to side effects like daytime drowsiness and the risk of dependence, prompting research into subunit-selective ligands (Engin et al., 2012, PMID: 22210311).

Other names

Benzodiazepine-sensitive GABA_A receptorBZ-sensitive GABA_A receptorIonotropic GABA receptorGABA(A) receptorGABA-A receptor

Positive allosteric modulation at the benzodiazepine binding site, located at the interface of the alpha (1, 2, 3, or 5) and gamma2 subunits, which increases the frequency of chloride channel opening upon GABA binding (Sigel & Steinmann, 2012, PMID: 22300836).