GABA-A R alpha 2: Small Molecules and Peptides

GABA A (γ-aminobutyric acid-type A) receptors are members of the cysteine-loop family of neurotransmitter-gated ion channels. GABA binding to A-type receptors induces anion-selective ion channel opening. These receptors are the principal fast inhibitory neurotransmitter receptors in the CNS. GABA A receptors are heteropentamer combinations of seven subunit types; α, β, γ, δ, ε, θ, and π. Three subunits, α, β, and γ, have at least three separate gene products in mammals, and typical GABA A receptors have some combination of α, β, and γ subunits.

The rat α2 isoform is a 53 kDa, 423 amino acid (aa), 4 transmembrane protein with two terminal extracellular regions. The ligand-binding region is in the N-terminus (aa 15 - 222). As with many receptors, phosphorylation is likely to be used as a regulatory mechanism. The α2 subunit is known to be phosphorylated on Ser/Thr residues. Rat α2 has multiple isoforms, all involving the 5' UTR. These may dictate α2 levels within the cell. This receptor subunit is particularly abundant in forebrain areas and is a potential target of anabolic steroids. Behavioral alterations associated with steroid abuse may be a manifestation of α2β3γ2L receptor activation.