Gamma-aminobutyric acid type A receptor alpha1-beta2-gamma2 subtype (GABAA receptor alpha1beta2gamma2)

The Gamma-aminobutyric acid type A (GABAA) receptor alpha1-beta2-gamma2 subtype is the most abundant inhibitory neurotransmitter receptor in the mammalian central nervous system (Sigel & Steinmann, 2012). It functions as a heteropentameric ligand-gated chloride channel that mediates fast inhibitory synaptic transmission (Olsen & Sieghart, 2008). The specific interface between the alpha1 and gamma2 subunits is of significant pharmacological importance as it constitutes the classic high-affinity binding site for benzodiazepines (Rudolph & Knoflach, 2011). Binding of drugs like benzodiazepines or non-benzodiazepine 'Z-drugs' to this interface acts as a positive allosteric modulator, increasing the frequency of channel opening in the presence of GABA (Sigel & Steinmann, 2012). This specific alpha1-containing subtype is primarily responsible for the sedative, hypnotic, and anticonvulsant properties of these medications, whereas alpha2 or alpha3 subtypes are more closely linked to anxiolysis (Rudolph & Knoflach, 2011). Clinically, this receptor is a primary target for treating insomnia, status epilepticus, and acute anxiety, though chronic modulation is associated with the development of tolerance and physical dependence (Nutt & Stahl, 2010). [Citations: Sigel & Steinmann (2012) J Biol Chem; Olsen & Sieghart (2008) Pharmacol Rev; Rudolph & Knoflach (2011) Nat Rev Drug Discov; Nutt & Stahl (2010) CNS Spectr.]

Other names

GABAA receptor alpha1beta2gamma2Benzodiazepine receptorBZD sitealpha1-containing GABAA receptoralpha1(+)gamma2(-) interfaceGABA(A) receptor alpha1 subunit-containing subtype

Positive allosteric modulation of GABA-induced chloride currents at the alpha1/gamma2 subunit interface