Gamma-aminobutyric acid type A receptor alpha-1 beta-1 gamma-2 (GABA_A receptor α1β1γ2)

The Gamma-aminobutyric acid type A (GABA_A) receptor α1β1γ2 is a heteropentameric ligand-gated ion channel that serves as a primary mediator of fast inhibitory neurotransmission in the mammalian central nervous system (Sigel & Steinmann, 2012, J Biol Chem). It is composed of two α1, two β1, and one γ2 subunits arranged around a central pore that is selective for chloride ions (Olsen & Sieghart, 2008, Pharmacol Rev). Upon the binding of the inhibitory neurotransmitter GABA, the receptor undergoes a conformational change that opens the pore, leading to chloride influx and subsequent hyperpolarization of the postsynaptic neuron (Jacob et al., 2008, Nat Rev Neurosci). This specific subunit configuration is a major target for several classes of clinically significant drugs, including benzodiazepines, which bind at the α/γ interface to enhance the receptor's response to GABA (Rudolph & Knoflach, 2011, Nat Rev Drug Discov). Dysregulation or mutations in the subunits of this receptor are linked to various neurological conditions, most notably epilepsy and anxiety disorders (Sieghart, 1995, Pharmacol Rev). Pharmacological modulation of the α1β1γ2 receptor is utilized to achieve sedation, muscle relaxation, and anticonvulsant effects, though chronic use is often limited by the development of tolerance and potential for dependence (Vinkers & Olivier, 2012, Adv Pharmacol Sci). Additionally, this receptor subtype is sensitive to general anesthetics like propofol and etomidate, which act as positive allosteric modulators or direct agonists at higher concentrations (Belelli et al., 2009, J Neurosci).

Other names

GABRA1-GABRB1-GABRG2 complexGABA(A) receptor alpha1beta1gamma2GABA-A receptor subunit alpha-1/beta-1/gamma-2Gamma-aminobutyric acid receptor subunit alpha-1/beta-1/gamma-2

Positive allosteric modulation of the chloride channel, increasing the frequency or duration of channel opening in response to GABA binding; direct agonism at high concentrations for certain anesthetics.