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

The Gamma-aminobutyric acid type A receptor subunit alpha 1 (GABRA1) is a critical component of the pentameric GABA-A receptor, the primary inhibitory neurotransmitter receptor in the mammalian central nervous system. Receptors containing the alpha 1 subunit are the most abundant GABA-A subtype in the brain and are primarily responsible for mediating the sedative, anticonvulsant, and amnestic effects of benzodiazepines and 'Z-drugs' like zolpidem (StatPearls, 2023; UniProt P14867). These receptors function as ligand-gated chloride channels; upon binding of GABA, the channel opens to allow chloride influx, hyperpolarizing the neuron and inhibiting action potential firing (PubMed: 29961021). Mutations in the GABRA1 gene are strongly linked to various forms of epilepsy, including juvenile myoclonic epilepsy and childhood absence epilepsy, due to impaired inhibitory signaling (NCBI Gene ID: 2554). Pharmacologically, alpha 1-selective modulators are widely utilized in the treatment of insomnia and acute seizures, though their use is often limited by side effects such as daytime sleepiness and the potential for abuse (PubChem CID: 5732).

Other names

GABA-A receptor alpha 1 subunitGABA(A) receptor subunit alpha-1GABRA1Gamma-aminobutyric acid receptor subunit alpha-1Alpha-1-containing GABA-A receptor

Positive allosteric modulation of the GABA-A receptor, increasing the frequency of chloride channel opening in response to GABA binding, which leads to hyperpolarization of the postsynaptic neuron and reduced neuronal excitability.