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目的研究咪唑安定对交感神经元全细胞钠通道电流的影响,探讨其循环抑制机制。方法酶消化法急性分离SD大鼠(8～12d)颈上交感神经节细胞 ,全细胞膜片钳技术记录咪唑安定对钠通道电流的影响。结果在钳制电压 -80mV,刺激电压0mV条件下 ,临床相关浓度的咪唑安定(0.3μmol·L -1)使钠通道电流峰值降低19.98 %(P<0.05) ,随浓度增加 ,抑制作用逐渐增强 ,50 %的钠通道电流峰值受抑制时的咪唑安定浓度 (IC50)约为18.35μmol·L-1;3μmol·L -1 的咪唑安定使钠电流稳态失活曲线产生明显的超极化方向移动(7.75mV ,P<0.05) ,用药前、后50 %的通道灭活时的条件脉冲电压 (V1/2)分别为 :-40.39mV、-48.14mV ;3μmol·L -1 的咪唑安定对钠电流的激活曲线几乎无影响。结论临床相关浓度的咪唑安定对交感神经节全细胞钠通道电流有明显的抑制作用,且主要与钠通道的失活有关。提示咪唑安定的循环抑制作用可能与其直接抑制交感神经有关。
Objective To investigate the effect of midazolam on the sodium channel current of sympathetic neurons and explore the mechanism of its inhibition. Methods The cervical sympathetic ganglion cells were isolated from SD rats (8 ~ 12 days) by enzymatic digestion method and the effect of midazolam on sodium channel current was recorded by whole-cell patch-clamp technique. Results With clinically relevant concentrations of midazolam (0.3 μmol·L -1) at a clamping voltage of -80 mV and a stimulation voltage of 0 mV, the peak current of sodium channel decreased by 19.98% (P <0.05). With increasing concentration, the inhibitory effect was gradually increased, 50% sodium channel current peak inhibition of the midazolam concentration (IC50) of about 18.35μmol·L-1; 3μmol·L -1 of midazolam sodium current steady-state inactivation curve significant hyperpolarization direction of movement (7.75mV, P <0.05). The pulse voltage (V1 / 2) of 50% channel inactivation before and after treatment were: -40.39mV, -48.14mV; The current activation curve has almost no effect. Conclusions Midazolam, a clinically relevant concentration, has a significant inhibitory effect on the sodium current in sympathetic ganglion cells, and is mainly related to inactivation of sodium channels. Tip midazolam cycle inhibition may be directly related to its inhibition of sympathetic.