Gamma-aminobutyric acid type A receptor alpha-2 beta gamma (GABA(A)R alpha2-beta-gamma)

The Gamma-aminobutyric acid type A (GABAA) receptor alpha-2 beta gamma complex is a heteropentameric ligand-gated ion channel that serves as a primary mediator of fast inhibitory neurotransmission in the mammalian central nervous system (1.3.1, 1.3.2). It is typically composed of two alpha-2 subunits, two beta subunits, and one gamma-2 subunit, which together form a chloride-selective pore (1.3.1, 1.3.4). Upon binding of the neurotransmitter GABA, the receptor undergoes a conformational change that allows chloride ions to flow into the neuron, resulting in membrane hyperpolarization and reduced neuronal excitability (1.1.2, 1.3.2). This specific receptor subtype is highly expressed in brain regions such as the hippocampus, amygdala, and striatum, where it plays a crucial role in regulating anxiety, emotional behavior, and muscle tone (1.3.3, 1.4.1). Unlike alpha-1-containing GABAA receptors, which are primarily responsible for the sedative and amnestic effects of benzodiazepines, alpha-2-containing receptors are the principal mediators of anxiolytic and analgesic actions (1.3.1, 1.4.1). Consequently, the alpha-2 beta gamma complex is a major therapeutic target for the development of subtype-selective positive allosteric modulators (PAMs) intended to treat anxiety disorders, epilepsy, and chronic pain with a reduced side-effect profile compared to traditional non-selective benzodiazepines (1.4.1, 1.4.3).

Other names

GABRA2-containing GABAA receptorAlpha-2-containing GABAA receptorBZ2 receptor siteGABRA2/GABRB/GABRG complexGamma-aminobutyric acid receptor subunit alpha-2 complex

Positive allosteric modulation of the GABA-A receptor chloride channel