GABA-A R alpha 4: 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 α4 isoform is a 67 kDa, 517 amino acid (aa), 4 transmembrane protein with two terminal extracellular regions. The ligand-binding region is in the N-terminus (aa 14 - 221). The α4 subunit is unusual in that it does not seem to preferentially form channel complexes with the gamma subunit. In hippocampal neurons, α4 subunits apparently form GABA receptors that do not cluster, but exist in diffuse networks in nonsynaptic membrane.