ALPHA-SUBUNIT ISOFORM INFLUENCES GABA(A) RECEPTOR MODULATION BY PROPOFOL

We have investigated the role of the alpha subunit in the modulation o f gamma-aminobutyric acid type A (GABA(A)) receptors by the general an esthetic propofol, using whole-cell patch clamp recordings made from d istinct stable fibroblast cell lines which expressed only alpha(1) bet a(3) gamma(2) or alpha(6) beta(3) gamma(2) GABAA receptors. At clinica lly relevant anesthetic concentrations, propofol potentiated submaxima l GABA currents in alpha(1) beta(3) gamma(2) receptors to a far greate r degree than those in alpha(6) beta(3) gamma(2), receptors. The alpha subunit influenced the efficacy of propofol for modulation, but not i ts 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 GAB A by trichloroethanol, and the potentiation and direct gating by metho hexital was also studied, and showed the same relative trends as propo fol. (C) 1997 Elsevier Science Ltd.