A role for the 2' residue in the second transmembrane helix of the GABA A receptor gamma2S subunit in channel conductance and gating

GABAA receptors composed of a, b and c subunits display a significantly higher single-channel conductance than receptors comprised of only a and b subunits. The pore of GABAA receptors is lined by the second transmembrane region from each of its five subunits and includes conserved threonines at the 6¢, 10¢ and 13¢ positions. At the 2¢ position, however, a polar residue is present in the c subunit but not the a or b subunits. As residues at the 2¢, 6¢ and 10¢ positions are exposed in the open channel and as such polar channel-lining residues may interact with permeant ions by substituting for water interactions, we compared both the single-channel conductance and the kinetic properties of wild-type a1b1 and a1b1c2S receptors with two mutant receptors, abc(S2¢A) and abc(S2¢V).