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目的 通过观察咪达唑仑对交感神经元全细胞N-型钙电流的影响,评价其对交感神经元的抑制作用。方法 用酶消化法获得急性分离的SD大鼠(7~10d)颈上交感神经节细胞,应用膜片钳技术记录不同浓度的咪达唑仑(0.1、0.3、3.0、10、50、100μmol/L)对N型钙电流的影响。结果在钳制电位(Vh)-80mV,刺激电压(Vt)-30mV~+10mV条件下,不同浓度的咪达唑仑对N-型钙电流均有抑制作用,且呈浓度依赖性(r=0.964P<0.01)。临床相关浓度的咪达唑仑(0.3μmol/L)使钙通道电流峰值下降35%(P<0.01)。50%钙通道电流峰值受抑制时的咪达唑仑浓度(IC50)约为4.25μmol/L。结论 临床相关浓度的咪达唑仑对交感神经元全细胞N-型钙电流有明显的抑制作用,提示咪达唑仑的循环抑制作用可能与抑制交感神经系统的活动有关。
Objective To observe the effect of midazolam on the whole cell N-type calcium current in sympathetic neurons and evaluate its inhibitory effect on sympathetic neurons. Methods Acutely isolated SD rat (7 ~ 10 days) of cervical sympathetic ganglion cells were isolated by enzymatic digestion. The midazolam of different concentrations (0.1, 0.3, 3.0, 10, 50 and 100 μmol / L) on the N-type calcium current. Results Different concentrations of midazolam had inhibitory effects on N-type calcium currents at the potentials (Vh) -80mV and stimulation voltage (Vt) -30mV ~ + 10mV in a concentration-dependent manner (r = 0.964 P <0.01). A clinically relevant concentration of midazolam (0.3 μmol / L) decreased the peak calcium channel current by 35% (P <0.01). The midazolam concentration (IC50) at 50% calcium channel peak inhibition was approximately 4.25 μmol / L. Conclusions Midazolam, a clinically relevant concentration, has a significant inhibitory effect on N-type calcium current in sympathetic neurons, suggesting that circulating inhibition of midazolam may be related to inhibition of sympathetic nervous system activity.