金雀花碱对大鼠心室肌细胞钠通道的影响

Effects of Cytisine on Sodium Channel Currents of Rats′ Ventricular Myocardial cells

目的研究金雀花碱(Cy)对大鼠心室肌细胞钠离子通道电流(INa)的影响,探索Cy在离子通道水平抗心律失常的作用机制。方法使用Langendorff恒温恒压灌流装置,单酶解法分离SD大鼠心室肌细胞,将心室肌细胞分为对照组、100μmol/L Cy组和300μmol/L Cy组。应用全细胞膜片钳记录技术,观察Cy对大鼠心室肌细胞INa的影响。结果Cy(≥100μmol/L)能显著抑制INa,其作用呈浓度依赖性。与对照组比较,100μmol/L和300μmol/L Cy可使INaⅠ~Ⅴ曲线明显上移,INa峰值由(-32.81±3.93)pA/pF依次降为(-21.77±4.07)pA/pF和(-14.8±2.99)pA/pF(P<0.01),但不改变其激活电位、峰电位和反转电位;使稳态失活曲线显著左移,半数失活电压V1/2降低(P<0.05,P<0.01);失活后恢复曲线显著右移,恢复时间常数γ延长(P<0.05,P<0.01)。结论Cy对大鼠心室肌细胞的INa呈浓度依赖性的抑制作用,并可改变其失活及失活后恢复动力学特征,可能是其抗心律失常的作用机制。

Objective To study the effects of cytisine on the sodium ion channel currents(INa)of ventricular myocardial cells in rats,and to explore its anti-arrhythmic mechanisms at the ion channel level.Methods Ventricular myocardial cells were enzymatically isolated from SD rats by Langendorff with constant pressure and temperature.The ventricular myocardial cells were divided into control group,100μmol/L cytisine group and 300μmol/L cytisine group.The whole-cell patch clamp techniques were used to observe the effects of Cy on sodium channel current of rat ventricular myocytes.Results Cytisine(≥100μmol/L)inhibited sodium current significantly in a concentration-dependent manner.Compared with the control group,theⅠ-Ⅴcurve of the sodium current was significantly up-shifted by 100μmol/L and 300μmol/L Cy,and the peak sodium current(-32.81±3.93)pA/pF was reduced to(-21.77±4.07)pA/pF and(-14.8±2.99)pA/pF(P<0.01),but the activation potential,peak potential and reverse potential did not change.Cy could significantly shift the steady-state inactivation curve to the left and reduce the half-inactivation voltage V1/2(P<0.05,P<0.01).Cy could significantly shift the recovery curve to the right and prolong the recovery time constantγvalue(P<0.05,P<0.01).Conclusion cytisine could significantly inhibit sodium current in a concentration-dependent manner,and could change the kinetics of inactivation and recovery after inactivation,which was probably related to its antiarrhythmic mechanisms.