Benoit E
Laboratoire de Physiologie Cellulaire, URA CNRS 1121, Université de Paris Sud, Orsay, France.
Eur J Anaesthesiol. 1995 Jan;12(1):59-70.
The effects of ketamine, etomidate, alphaxalone and alphadolone acetate on nodal sodium and potassium currents of frog myelinated nerve fibre have been examined. The four general anaesthetics reversibly depressed ionic currents, although they tended to be more effective in blocking potassium than sodium current. The potassium current was reduced by etomidate and alphaxalone in a time-dependent manner. This was not found for ketamine and alphadolone acetate. In addition to blocking effects on sodium current, etomidate, alphaxalone and alphadolone acetate, but not ketamine, induced a negative shift of steady-state sodium inactivation-voltage curves. Collectively, the general anaesthetics appeared to alter specifically and differentially sodium and potassium channel-gating systems. The simplest interpretation of these results suggests that the compounds produce state-dependent blocks of ionic channels, and that there are general anaesthetic receptor sites located on the channel proteins themselves. Furthermore, potassium and sodium channels may contain several types of receptor sites, through which anaesthetics could exert their different actions.
已研究了氯胺酮、依托咪酯、α-羟孕酮和醋酸α-孕甾二酮对青蛙有髓神经纤维节点钠电流和钾电流的影响。这四种全身麻醉药可逆性地抑制离子电流,尽管它们在阻断钾电流方面往往比钠电流更有效。依托咪酯和α-羟孕酮可使钾电流呈时间依赖性降低。氯胺酮和醋酸α-孕甾二酮未出现这种情况。除了对钠电流的阻断作用外,依托咪酯、α-羟孕酮和醋酸α-孕甾二酮(而非氯胺酮)可使稳态钠失活电压曲线发生负向移位。总体而言,全身麻醉药似乎特异性地、差异性地改变钠通道和钾通道门控系统。对这些结果最简单的解释表明,这些化合物产生离子通道的状态依赖性阻断,且通道蛋白本身存在全身麻醉药受体位点。此外,钾通道和钠通道可能含有几种类型的受体位点,麻醉药可通过这些位点发挥不同作用。