摘要
目的研究咪达唑仑对大鼠单一心室肌细胞ATP敏感性钾电流(IKATP)的作用。方法急性酶解法分离大鼠心室肌细胞,利用膜片钳制技术全细胞记录法,设保持电位为-40mV,指令电位为-100～+40mV,步阶脉冲20mV,波宽200ms,刺激间隔6s的方波钳制方案进行刺激。结果咪达唑仑能够开放心室肌细胞ATP敏感性钾(KATP)通道,在一定范围内具有剂量依赖性关系。指令电位在-60mV时,咪达唑仑(0.3～10μmol/L)可使KATP通道开放率分别增加至给药前的(119±5)%,(121±4)%和(121±6)%(P<0.01,n=9)。更高浓度(50～100μmol/L)咪达唑仑使KATP通道开放率略有下降,其他指令电位下的IKATP改变也符合此趋势。结论咪达唑仑对大鼠单一心室肌细胞KATP通道具有开放作用,这可能是其发挥心脏保护的机制之一。
Objective To investigate the effect of midazolam on ATP-sensitive K＋ currents（IKATP）in single ventricular myocytes of rats.Methods Single ventricular myocytes of rats were isolated with enzymatic dissociation technique.Whole-cell patch clamp technique was used.The stimulating protocol was：holding potential-40 mV,command potential-100 mV to ＋40 mV,step potential ＋20 mV,duration 200 ms,stimulating interval 6 s.Results Midazolam opened the ATP-sensitive K＋（KATP）channel by a dose-dependent manner within a range of concentrations.When the commanding potential was-60 mV,midazolam（0.3～10 μmol/L）increased the open rate of KATP channel to（119±5）%,（121±4）% and（121±6）%（P0.01,n=9）of control,respectively.Higher concentrations of midazolam（50～100 μmol/L）decreased the open rate slightly.The changes of IKATP under other command potentials were consistent with this.Conclusion Midazolam opens KATP channel in single ventricular myocytes of rats,which may be one of the mechanisms of its cardiac protection effect.
基金
国家自然科学基金(30971181)
关键词
咪达唑仑
质子转运ATP酶类
心室肌
膜片钳术
Midazolam
Proton-translocating ATPases
Ventricular muscle
Patch-clamp techniques
