参松养心胶囊对心室肌细胞钾通道的影响

The effect of Shensongyangxin capsule on potassium channel currents in isolated ventricular myocytes

目的观察参松养心胶囊干粉提取溶液对大鼠单个心室肌细胞内向整流钾电流(IK1)、瞬时外向钾电流(Ito)以及豚鼠心肌细胞延迟整流钾电流(Ik)的影响。方法用酶解法分离单个心室肌细胞,并用全细胞膜片钳记录技术。结果当药物浓度0.5%时,可以使大鼠心肌细胞IK1内向成分降低,使-100mV时IK1电流密度从(-10.8±1.8)pA/pF降至(-7.2±2.1)pA/pF,平均抑制率为(33.1±16.9)%(n=11,P<0.05),但不改变电流的翻转电位及整流特性。药物同时对Ito电流的瞬时成分有抑制作用,60mV时Ito电流密度从(-19.8±7.1)pA/pF降至(-10.0±3.9)pA/pF,平均抑制率为(50.6±10.8)%(n=6,P<0.05),稳态失活曲线左移,失活后恢复时间常数增大。药物浓度0.5%时,对Ik有电压依赖性抑制作用,50mV时对尾电流峰值的抑制率为(30.8±1.1)%(n=5,P<0.05)。结论参松养心胶囊干粉提取溶液对IK1,Ito和Ik均具有不同程度的阻滞作用。这种多离子通道阻滞作用不仅使参松养心胶囊具有广谱的抗心律失常疗效,减少致心律失常的副作用,对Ito的阻滞效应还将显示其独特的抑制2相折返的作用,值得对其作更深入和广泛的研究。

Objective To investigate the effect of Shensonyangxincapsule on inward rectifier potassium currents （ ⅠK1 ）, transient outward potassium current （ Ⅰto ） and delayed rectifier current （ Ⅰk ） in ventricular myecytes. Methods Whole cell patch- clamp technique was used to observe potassium currents in enzymatieally isolated ventrieular myocytes of rat or guinea-pig.Results Shensongyangxin capsule decreased the inward current of ⅠK1 by 33.1% when test potential was - 100 mV,but which had little effect on the reversal potential and the rectified property. The drug also inhibited the transient component of Ⅰto by 50.6 % at 60 mV while which shifted the inactive curve negatively and prolonged the recovery time after channel inactivation. The density of Ⅰk tail current was decreased by 30.77±1.11% （ n = 5, P 〈 0.05） at 50 mV after the drug was used. Conclusion Shensongyangxin capsule can block Ⅰk1 , Ⅰto and Ⅰk ,which may contribute to its anti-arrhythmie effect. The inhibitive effect on multiple channels might possess the broad-spectrum of antiarrhythmie effects and reduce the possibility of proarrhythmia. For the inhibition of Ⅰto, which suggests the possible unique effect on suppression of phase 2 reentry, deserves more intensive investigation.