Pregnenolone sulphate and Zn²⁺ inhibit recombinant <i>rat</i> GABA_A receptor through different channel property

Abstract

Pregnenolone sulphate was a gamma2-subunit independent inhibitor in the GABA(A) receptor, whereas the Zn(2+) antagonism was profoundly influenced by the gamma2-subunit. It is likely that the 2' residue closest to the N-terminus of the protein at M(2) helix on both alpha1 and beta2 subunit are critical to the inhibitory actions of PS and the function of Cl(-) channels. These results are consistent with the hypothesis that PS behaves as a Cl(-) channel blocker that does not share with Zn(2+), the coincident channel property in the GABA(A) receptors.