Effects of γ2S subunit incorporation on GABA A receptor macroscopic kinetics

Abstract

GABA A receptors, the major inhibitory neurotransmitter receptors in the mammalian central nervous system, are heteropentameric proteins. We are interested in understanding the contribution of the γ subunit to the kinetic properties of GABA A receptors. Studies in Xenopus oocytes have suggested that co-expression of α1, β2, and γ2S subunits results in the formation of both αβ and αβγ receptors ( Boileau et al., 2002a; Boileau et al., 1998). Here, we have used an excess of the γ2S subunit in transfections of HEK293 cells to bias expression toward αβγ-containing receptors. Using rapid application and whole cell patch clamp techniques, we found that incorporation of the γ subunit eliminated the rapid phases of desensitization and accelerated deactivation, consistent with a proposed role of desensitization in slowing deactivation. In addition, αβγ receptors had an increased GABA EC 50, reduced sensitivity to block by Zn 2+, and did not display outward rectification as compared to αβ receptors.