Effects of γ2S subunit incorporation on GABAA receptor macroscopic kinetics

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 gamma subunit to the kinetic properties of GABAA receptors. Studies in Xenopus oocytes have suggested that co-expression of alpha1, beta2, and gamma2S subunits results in the formation of both alphabeta and alphabetagamma receptors (Boileau et al., 2002a; Boileau et al., 1998). Here, we have used an excess of the gamma2S subunit in transfections of HEK293 cells to bias expression toward alphabetagamma-containing receptors. Using rapid application and whole cell patch clamp techniques, we found that incorporation of the gamma subunit eliminated the rapid phases of desensitization and accelerated deactivation, consistent with a proposed role of desensitization in slowing deactivation. In addition, alphabetagamma receptors had an increased GABA EC50, reduced sensitivity to block by Zn2+, and did not display outward rectification as compared to alphabeta receptors. (C) 2003 Elsevier Science Ltd. All rights reserved.