GABA (γ-aminobutyric acid) is the major inhibitory neurotransmitter in the brain. Its production, release, reuptake and metabolism occur in the nervous system.¹

The GABA transmitter interacts with two major types of receptors: ionotropic GABA(A) and metabotropic GABA(B) receptors. The GABA(A) receptor belongs to the ligand gated ion channel superfamily.²

The GABA(A) R, is a heteropentamer, with all of its five subunits contributing to the pore formation.

To date, eight subunit isoforms were cloned: α, β, γ, δ, ε, π, θ, and ρ.¹ Six α subunit isoforms were described to exist in mammals (α1-α6). The native GABA(A) receptor, in most cases, consists of 2α, 2β and 1γ subunit. The α subunit is the most common subunit and is expressed ubiquitously. It determines the affinities for allosteric ligands shown by GABA(A)R.

A possible role for the GABA(A) receptors in alcohol action has been derived from animal studies, in vitro cell models and human research which suggested an important role for GABA(A) α6 along with β2, α1 and γ2, in alcohol related phenotypes.³

In Canavan disease (inherited leukodystrophy), low level of expression of GABA(A) α6 was reported.⁴