Gamma-aminobutyric acid type A receptor alpha 1 subunit-containing receptor (GABA_A receptor α1)

Gamma-aminobutyric acid type A (GABA_A) receptors containing the α1 subunit are the most prevalent subtype of inhibitory ligand-gated ion channels in the mammalian central nervous system [1, 6]. These receptors typically exist as pentameric complexes, most commonly in an α1β2γ2 stoichiometry, and are primarily located at postsynaptic sites where they mediate fast phasic inhibition [9, 11]. Upon binding of the neurotransmitter GABA, the receptor undergoes a conformational change that opens a central chloride-selective pore, leading to hyperpolarization of the neuron and a reduction in excitability [1, 12]. This specific subunit configuration is highly sensitive to benzodiazepines and is the primary target for "Z-drugs" like zolpidem, which exhibit selectivity for α1-containing receptors to induce hypnotic effects [1, 4]. Mutations in the GABRA1 gene, which encodes the α1 subunit, are clinically linked to various epilepsy syndromes, including juvenile myoclonic epilepsy and generalized epilepsy with febrile seizures plus (GEFS+) [2, 3]. Pharmacological modulation of these receptors is a cornerstone in treating insomnia, anxiety, and acute seizures, although chronic use is limited by risks of sedation, tolerance, and physical dependence [12, 18].

Other names

GABRA1-containing GABA_A receptorAlpha-1 subunit-containing GABA_A receptorGABRA1GABA(A) receptor subunit alpha-1EJMEJM5ECA4DEE19

Positive allosteric modulation (PAM) at the benzodiazepine binding site (α/γ interface), increasing chloride ion conductance and neuronal hyperpolarization.