θ, a novel γ-aminobutyric acid type A receptor subunit

γ-Aminobutyric acid type A (GABA-A) receptors are a major mediator of inhibitory neurotransmission in the mammalian central nervous system, and the site of action of a number of clinically important drugs. These receptors exist as a family of subtypes with distinct temporal and spatial patterns of expression and distinct properties that presumably underlie a precise role for each subtype. The newest member of this gene family is the θ subunit. The deduced polypeptide sequence is 627 amino acids long and has highest sequence identity (50.5%) with the β1 subunit. Within the rat striatum, this subunit coassembles with α2, β1, and γ1, suggesting that γ-aminobutyric acid type A receptors consisting of arrangements other than αβ + γ, δ, or ɛ do exist. Expression of α2β1γ1θ in transfected mammalian cells leads to the formation of receptors with a 4-fold decrease in the affinity for γ-aminobutyric acid compared with α2β1γ1. This subunit has a unique distribution, with studies so far suggesting significant expression within monoaminergic neurons of both human and monkey brain.