Gamma-aminobutyric acid A receptor subunit alpha-1 (GABAA receptor alpha-1 (GABRA1))

Gamma‑aminobutyric acid A receptor subunit alpha‑1 is a protein component of the pentameric ligand-gated ion channels known as GABAA receptors. These receptors mediate fast inhibitory neurotransmission in the central nervous system by allowing chloride ions to flow into neurons upon activation by their endogenous ligand γ‑aminobutyric acid (GABA), leading to hyperpolarization and reduced neuronal excitability. The α₁ subunit is one of several possible α-subunits but is among the most widely expressed in human brain. It combines most commonly with β₂/β₃ and γ₂ subunits to form functional synaptic receptors that are key targets for sedative-hypnotics such as benzodiazepines and non-benzodiazepine hypnotics like zolpidem. The pharmacology depends on its specific combination with other subunits; α₁-containing receptors mediate many classical sedative effects. Mutations in its gene can cause various forms of genetic epilepsy. As a major mediator of inhibition in brain circuits—and a target for numerous therapeutic agents—it plays critical roles both physiologically and pathologically.

Other names

GABA(A) receptor subunit alpha-1GABA(A) receptor, alpha 1GABAA alpha 1GABAAR alpha1GABAAR subunit alpha-1gamma-aminobutyric acid A receptor, alpha 1gamma-aminobutyric acid (GABA) A receptor, alpha 1gamma-aminobutyric acid (GABA-A) receptor, subunit alpha 1ECA4EIEE19EJMEJM5GABRA1

Drugs targeting this molecule act via several mechanisms including: – Positive allosteric modulation at the benzodiazepine binding site to enhance chloride influx and inhibitory signaling (benzodiazepines) — Direct agonism at the orthosteric site to activate the chloride channel directly (e.g., muscimol) — Prolongation of channel opening duration or frequency by barbiturates or other modulators