Mody I, Tanelian D L, MacIver M B
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA 94305.
Brain Res. 1991 Jan 11;538(2):319-23. doi: 10.1016/0006-8993(91)90447-4.
Whether the major action of anesthetics is to depress the central nervous system (CNS) by reducing excitation or enhancing inhibition remains unknown. Using whole cell patch-clamp recording in hippocampal slices, halothane and pentobarbital were found to prolong the decay time constant (TAU(D)) of GABAA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs). Intracellular administration of the Ca2+ chelator BAPTA or the Ca2+ release inhibitor dantrolene significantly (ANOVA, P less than 0.005) reduced halothane's effect; in contrast, the pentobarbital effect was unchanged. Halothane induced depression of population spike amplitude was blocked by the GABAA antagonist bicuculline. Together, these findings suggest that a major depressant effect of halothane involves enhancement of GABAA-mediated inhibition through release of intraneuronally stored Ca2+.
麻醉剂的主要作用是通过减少兴奋或增强抑制来抑制中枢神经系统（CNS），这一点仍不清楚。在海马切片中使用全细胞膜片钳记录，发现氟烷和戊巴比妥可延长GABAA介导的自发性抑制性突触后电流（sIPSCs）的衰减时间常数（TAU(D)）。细胞内注射Ca2+螯合剂BAPTA或Ca2+释放抑制剂丹曲林可显著（方差分析，P<0.005）降低氟烷的作用；相比之下，戊巴比妥的作用未改变。GABAA拮抗剂荷包牡丹碱可阻断氟烷诱导的群体峰电位幅度降低。这些研究结果共同表明，氟烷的主要抑制作用涉及通过释放神经元内储存的Ca2+增强GABAA介导的抑制作用。
