alpha subunit isoform influences GABA(A) receptor modulation by propofol

We have investigated the role of the alpha subunit in the modulation of gamma-aminobutyric acid type A (GABA(A)) receptors by the general anesthetic propofol, using whole-cell patch clamp recordings made from distinct stable fibroblast cell lines which expressed only alpha(1) beta(3) gamma(2) or alpha(6) beta(3) gamma(2) GABAA receptors. At clinically relevant anesthetic concentrations, propofol potentiated submaximal GABA currents in alpha(1) beta(3) gamma(2) receptors to a far greater degree than those in alpha(6) beta(3) gamma(2), receptors. The alpha subunit influenced the efficacy of propofol for modulation, but not its potency. In contrast, direct gating of the ion channel by propofol, in the absence of GABA, was significantly larger in the alpha(6) than the alpha(1) containing receptors. The potentiation of submaximal GABA by trichloroethanol, and the potentiation and direct gating by methohexital was also studied, and showed the same relative trends as propofol. (C) 1997 Elsevier Science Ltd.