Benoit E, Carratù M R, Dubois J M, Mitolo-Chieppa D, Preziosi P
Br J Pharmacol. 1987 Jan;90(1):7-14. doi: 10.1111/j.1476-5381.1987.tb16819.x.
The effects of the general anaesthetic etomidate (0.1 to 1 mM) upon the node of Ranvier of frog isolated nerve fibres were investigated under current and voltage clamp conditions. When added to the external solution, etomidate reversibly decreased the amplitude of the action potential. The action potential block, induced by the drug, was reversed by increasing the membrane potential. Etomidate rapidly and reversibly blocked the Na current with an apparent dissociation constant of 0.6 mM. In the presence of the drug, the steady-state inactivation-voltage curve of the Na current was shifted towards negative voltages. The block of Na current by etomidate was partially removed by repetitive depolarization preceded by a 50 ms period of hyperpolarization. In contrast, the block was enhanced when the repetitive depolarization was not preceded by hyperpolarization. This suggests that Na channels were preferentially blocked by the drug in the inactivated state. The K current was reversibly blocked by etomidate with an apparent dissociation constant of 0.2 mM. In the presence of the drug, the K current showed an apparent fast inactivation suggesting that K channels were blocked in the open state. We conclude that at higher concentrations than those attainable in the mammalian brain following single anaesthetic doses the general anaesthetic etomidate has a "local anaesthetic-like' action on the peripheral nervous system.
在电流钳和电压钳条件下，研究了全身麻醉药依托咪酯（0.1至1 mM）对青蛙离体神经纤维郎飞结的影响。将依托咪酯添加到外部溶液中时，它会可逆地降低动作电位的幅度。药物诱导的动作电位阻滞可通过增加膜电位来逆转。依托咪酯迅速且可逆地阻断钠电流，其表观解离常数为0.6 mM。在药物存在下，钠电流的稳态失活-电压曲线向负电压方向移动。依托咪酯对钠电流的阻滞可通过在50毫秒超极化期之前进行重复去极化而部分消除。相反，当重复去极化之前没有超极化时，阻滞作用增强。这表明钠通道在失活状态下优先被药物阻断。钾电流被依托咪酯可逆地阻断，其表观解离常数为0.2 mM。在药物存在下，钾电流表现出明显的快速失活，表明钾通道在开放状态下被阻断。我们得出结论，在单次麻醉剂量后高于哺乳动物大脑所能达到的浓度时，全身麻醉药依托咪酯对外周神经系统具有“局部麻醉样”作用。
