摘要
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。
Aim The effects of midazolam on the whole-cell sodium currents in rat sympathetic neurons were studied to explore the mechanisms where by midazolam mediates hypotension. Methods Whole-cell patch-clamp recordings were performed on enzymatically isolated rat superior cervical sympathetic neurons. Results Midazolam dose-dependently blocked the whole-cell sodium currents evoked by a voltage step to 0 mV from a holding potential of -80 mV with a mean drug concentration required to produce 50% current inhibition (IC50) values of 18.35 μmol·L-1; Clinically relevant concentration of midazolam(0.3 μmol·L-1) reduced sodium peak currents by 19.98%(P<0.05); 3 μmol·L-1 midazolam didn't affect the shape of I-V curves of sodium currents, but reduced the peak values by 21.75% . Similarly, 3 μmol·L-1 midazolam didn't cause significant shift in the voltage-dependence of activation curve either. However,3 μmol·L-1 midazolam caused a substantial hyperpolarizing shift of the steady-state inactivation curve (7.75 mV, P<0.05), that is the conditioning pulse potential at whih half- maximal channel is inactivated (V1/2) was changed from -40.39 mV to -48.14 mV. Conclusion Clinically relevant concentration of midazolam has significant inhibition on sympathetic neurons.This inhibition is dose-dependent and relavant to the inactivation of sodium channel. The circulation depression of midazolam may be relevant to the direct suppresion of sympathetic neurons.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2000年第2期108-111,共4页
Chinese Journal of Clinical Pharmacology and Therapeutics
关键词
咪唑安定
交感神经节
钠通道
膜片钳
midazolam
sympathetic ganglion
sodium channel
patch-clamp
