Alpha Subunit Position and GABA Receptor Function

GABA A (γ-aminobutyric acid type A) receptors are ligand-gated ion channels composed of five subunits, generally two αs, two βs, and a γ2. Recent research in which sets of subunits containing α1 or α6 subunits were artificially linked has revealed the importance of subunit position in determining GABA A receptor function. Sensitivity to benzodiazepines depended on juxtaposition of an α1 subunit with the γ2 subunit, whereas sensitivity to furosemide depended only on the presence of an α6 subunit and not on its specific location. The major utility of the linked subunit approach is to provide a mechanism for discovering the functional signatures of defined subunit arrangements, and thus a route to identifying such arrangements in vivo.