Gamma-aminobutyric acid type A receptor alpha1beta2gamma2S (GABAAR α1β2γ2S) (GABAAR α1β2γ2S)

The GABAA receptor α1β2γ2S is the most abundant isoform of the gamma-aminobutyric acid type A (GABAA) receptor in the mammalian central nervous system [1, 2]. It is a heteropentameric ligand-gated ion channel composed of two α1, two β2, and one γ2S (short splice variant) subunits arranged around a central chloride-conducting pore [1, 9]. This receptor mediates fast inhibitory neurotransmission, known as phasic inhibition, by allowing chloride ions to flow into the postsynaptic neuron upon GABA binding, which hyperpolarizes the cell and reduces its excitability [1, 10]. It is a major therapeutic target for several classes of drugs, including benzodiazepines, which bind at the interface of the α1 and γ2 subunits to act as positive allosteric modulators [1, 3]. These drugs are used clinically to treat anxiety, insomnia, and seizures, and to induce anesthesia [3, 12]. However, chronic use can lead to tolerance and physical dependence, and excessive activation may cause respiratory depression or cognitive impairment [1, 12].

Other names

GABAA receptor alpha1beta2gamma2Sα1β2γ2S GABA receptorGABRA1-GABRB2-GABRG2S complexGABA(A) receptor alpha1beta2gamma2SGamma-aminobutyric acid type A receptor alpha1-beta2-gamma2S

The GABAA receptor α1β2γ2S functions as a ligand-gated chloride channel. Drugs targeting this receptor typically act as positive allosteric modulators (PAMs). Benzodiazepines bind to the extracellular interface between the α1 and γ2 subunits, increasing the frequency of channel opening in the presence of GABA [1, 14]. Barbiturates and certain anesthetics bind to distinct sites (often within the transmembrane domain) to increase the duration of channel opening [1, 14]. These actions enhance the influx of chloride ions, leading to hyperpolarization of the postsynaptic neuron and a reduction in its firing rate, which produces sedative, anxiolytic, and anticonvulsant effects [1, 10].