卡维地洛对大鼠心室肌细胞钠通道的影响

目的研究卡维地洛对大鼠心室肌细胞膜钠通道的影响,在离子通道水平探讨卡维地洛的抗心律失常作用机制。方法用急性酶解法获得单个大鼠心室肌细胞,标准的全细胞膜片钳技术记录钠通道电流。结果①卡维地洛呈浓度依赖性抑制钠通道电流,IC50=(6.35±0.40)μmol·L-1。②10μmol·L-1卡维地洛能使心肌细胞钠通道电流-电压关系曲线明显上移,峰电流从(17.31±1.68)pA/pF减少至(6.58±1.35)pA/pF(n=8,P<0.05),激活电位、峰电位和翻转电位无明显改变。③卡维地洛能使钠通道电流失活曲线明显左移。④卡维地洛对钠通道电流的激活和复活曲线无明显影响。⑤卡维地洛呈频率依赖性地抑制钠通道电流。⑥1μmol·L-1卡维地洛能明显阻断10μmol·L-1异丙肾上腺素增加钠通道电流效应。结论卡维地洛能够抑制心肌细胞钠通道电流,呈浓度依赖性和频率依赖性。

Effect of carvedilol on sodium channel current in isolated ventricular myocytes of rats

Aim To determine the effect of carvedilol on sodium channel in islated ventricular myocytes of rats; to explore the mechanism of carvedilol at the ionic channel level.Methods Single ventricular myocytes of rats were isolated by enzymatic dissociation. The whole-cell patch-clamp recording technique was used to record the change of sodium channel current influenced by carvedilol. Result: Carvedilol decreased the sodium channel current in a dose-dependent and voltage-dependent manner in ventricular myocytes of rats,the IC_ 50 was 6.35 μmol·L -1.①The current-voltage curve was shifted upwards,with in no significant changes active potential,peak potential and reverse potential.②The inactivation curve was shifted to morenegative potential, but the activation curve and the recovery curve were not altered.③The suppression of sodium channel was enhanced with an increase in the frequency of stimuli, showing a positive rate-dependence. ④Carvedilol blocked the effect of 10 μmol·L -1 isoproterenol which increased sodium current. Conclusion Carvedilol concentration-dependently decreased sodium channel current in ventricular myocytes of rat.