A third g subunit of the g-aminobutyric acid type A receptor family

Cloned cDNAs encoding a member of the &gamma:-aminobutyric acid type A receptor &gamma:-subunit class were isolated from rat-brain-mRNA-derived libraries. The γ3 mRNA is present in cortex, claustrum, caudate putamen, and some thalamic nuclei, particularly the medial geniculate nucleus, where it is the predominant &gamma:-subunit transcript. The γ3 gene is expressed at very low levels in cerebellum and hippocampus. In coexpression experiments with the α1 and ?2 subunits, &gamma:3 imparts benzodiazepine binding to &gamma:-aminobutyric acid type A receptors and forms γ-aminobutyric acid-gated benzodiazepine-modulated chloride channels that exhibit a larger conductance than α12 receptor channels. Furthermore, the presence of &gamma:3 in place of γ2 in α12γ receptors generates a marked decrease in the affinity of agonists while leaving the affinity of antagonists or negative modulators largely unaffected