Gamma-aminobutyric acid type A receptor alpha-1 beta-2 gamma-2L (GABA_A receptor α1β2γ2L) (GABA_A receptor α1β2γ2L)

The Gamma-aminobutyric acid type A (GABA_A) receptor alpha-1 beta-2 gamma-2L is a heteropentameric ligand-gated ion channel that serves as the primary mediator of fast inhibitory neurotransmission in the central nervous system (Sigel & Steinmann, 2012, Pharmacol. Rev.). This specific isoform, composed of α1, β2, and γ2L subunits, represents the most prevalent GABA_A receptor subtype in the human brain and is a critical target for various pharmacological agents (Olsen & Sieghart, 2008, Pharmacol. Rev.). Upon binding the endogenous neurotransmitter GABA, the receptor undergoes a conformational change that opens an integral chloride-selective pore, leading to membrane hyperpolarization and decreased neuronal firing (Jacob et al., 2008, Nat. Rev. Neurosci.). This receptor complex is the primary site of action for benzodiazepines, which bind at the α/γ interface to enhance the receptor's response to GABA (Tan et al., 2011, Nature). Clinically, it is targeted to treat conditions such as anxiety, insomnia, and epilepsy, though its modulation is associated with risks of sedation, tolerance, and dependence (Rudolph & Knoflach, 2011, Nat. Rev. Drug Discov.). The γ2L variant specifically includes a phosphorylation site for protein kinase C, which plays a role in the intracellular regulation and trafficking of the receptor (Moss et al., 1992, J. Biol. Chem.). Alpha-1 containing receptors are particularly associated with the sedative and anticonvulsant effects of benzodiazepines, making them a focus for sedative-hypnotic drug development (Rudolph et al., 1999, Nature). Antagonists like flumazenil can bind to the same site to reverse the effects of modulators, providing a mechanism for treating benzodiazepine overdose (Hoffman & Warren, 1993, Clin. Pharmacokinet.).

Other names

GABAA receptor alpha-1 beta-2 gamma-2LGABRA1-GABRB2-GABRG2L receptorBenzodiazepine-sensitive GABA receptorGABA(A) receptor alpha1beta2gamma2L

Positive allosteric modulation of the chloride channel opening frequency or duration upon GABA binding (Sigel & Steinmann, 2012, Pharmacol. Rev.).