Gamma-aminobutyric acid type A receptor alpha-1 beta-2 gamma-2 (GABA(A) receptor α1β2γ2)

The Gamma-aminobutyric acid type A (GABA-A) receptor alpha-1 beta-2 gamma-2 is the most abundant GABA-A receptor subtype in the adult mammalian brain, representing approximately 40% of all GABA-A receptors [PubMed, 21750098]. It is a heteropentameric ligand-gated ion channel composed of two alpha-1, two beta-2, and one gamma-2 subunit arranged around a central chloride-conducting pore [UniProt, P14867]. This receptor mediates fast inhibitory synaptic transmission; when the neurotransmitter GABA binds, the channel opens to allow chloride influx, hyperpolarizing the neuron and reducing the likelihood of an action potential [PubMed, 11447329]. The alpha-1 beta-2 gamma-2 configuration is particularly significant because it contains the classic benzodiazepine binding site at the interface of the alpha-1 and gamma-2 subunits [PubMed, 29973724]. Drugs such as benzodiazepines and non-benzodiazepine hypnotics (Z-drugs) act as positive allosteric modulators here, enhancing the inhibitory effects of GABA to treat insomnia, anxiety, and seizures [StatPearls, NBK513311]. Due to its widespread expression, pharmacological targeting of this receptor can lead to side effects like sedation, ataxia, and potential for abuse or dependence [PubMed, 15053703]. It serves as a critical therapeutic target for central nervous system depression and modulation of consciousness [PubMed, 21750098].

Other names

GABRA1-GABRB2-GABRG2 receptorBenzodiazepine-sensitive GABA(A) receptorAlpha-1-beta-2-gamma-2 GABA-A receptorGABRA1/GABRB2/GABRG2 complex

Positive allosteric modulation at the benzodiazepine binding site (alpha-gamma interface) which increases the frequency of chloride channel opening in response to GABA binding [StatPearls, NBK526124].