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

The Gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1) is a critical protein component of the GABA-A receptor, which serves as the primary inhibitory neurotransmitter receptor in the mammalian central nervous system [2, 14]. As a member of the Cys-loop family of ligand-gated ion channels, GABRA1 typically assembles with beta and gamma subunits to form a pentameric chloride channel that mediates fast phasic inhibition at synapses [6, 14]. Upon binding of the neurotransmitter GABA, the channel opens to allow chloride ion influx, leading to neuronal hyperpolarization and the suppression of action potential firing [1, 15]. GABRA1-containing receptors are the most abundant GABA-A subtype in the brain and are the principal targets for several major drug classes, including benzodiazepines and non-benzodiazepine hypnotics like zolpidem, which act as positive allosteric modulators [10, 14]. Mutations in the GABRA1 gene are strongly associated with genetic epilepsies, such as juvenile myoclonic epilepsy and childhood absence epilepsy, due to the resulting impairment in inhibitory signaling [6, 8]. While pharmacological activation of this target is essential for treating insomnia, anxiety, and acute seizures, chronic modulation is associated with significant safety concerns, including sedation, cognitive impairment, and the risk of tolerance and physical dependence [13, 15].

Other names

GABA(A) receptor subunit alpha-1 [6]GABAAR subunit alpha-1 [6]GABRA1 [4]ECA4 [4]EIEE19 [4]EJM [4]EJM5 [4]DEE19 [4]

Positive allosteric modulation, Agonism, Antagonism, and Channel blocking [3, 10, 14]