Four amino acid exchanges convert a diazepam-insensitive, inverse agonist-preferring GABAA receptor into a diazepam-preferring GABAA receptor

Benzodiazepines (BZ) exert their effects through GABA A receptors, which belong to the superfamily of ligand-gated ion channels. Coexpression of recombinant α, β, and γ subunits in a cell culture system mimics the BZ binding sites. The a variants largely determine the nature of the BZ binding site in such αiβjγk heteromultimers (i=1-6; j=1-3; k=1-3). Notably, the α1 and α6 variants confer high and low affinity for BZ agonists to the resulting receptor subtype, respectively. Glycine/glutamate and histidine/arginine positions in the a subunits of αxβ2γ2 receptors are involved in BZ I versus BZ II type selectivity