福辛普利对缺氧复氧豚鼠心室肌细胞动作电位及其离子通道的影响

 目的观察福辛普利预处理对缺氧复氧豚鼠心室肌细胞动作电位(AP)、L-型钙通道电流(ICa-L)和ATP敏感钾通道电流(I_K-ATP)的影响,探讨其抗再灌注性心律失常的电生理机制。方法采用全细胞电流钳和膜片钳技术分别记录AP和ICa-L,I_K-ATP。结果缺氧复氧使心室肌细胞AP时程(APD₅₀,APD₉₀)缩短;ICa-L峰值降低,I-V曲线上移,激活曲线右移,半数激活电压(V_1/2)增大,失活曲线左移,失活V_1/2减低;ATP敏感钾通道由正常关闭状态到完全开放。与缺氧复氧组相比,福辛普利预处理使APD₅₀,APD₉₀相对延长;ICa-L峰值增加,I-V曲线上移幅度减小,激活曲线左移,失活曲线右移,激活与失活V_1/2均接近正常,ATP敏感钾通道进一步开放,电流明显增加。结论福辛普利预处理能显著改善缺氧复氧状态下L-钙通道的抑制状态,促进动作电位参数的恢复,减少有效不应期的离散度及折返形成;通过药物预适应机制,进一步开放ATP敏感钾通道,增加ATP敏感钾电流,而发挥抗再灌注心律失常的作用。

Effects of Fosinopril on Action Potential and Ion Channels in Guinea Pig Ventricular Myocytes Undergone Anoxia-reoxygenation Injury

OBJECTIVE To study the electrophysiological mechanism of fosinopril anti-arrhythmia effect during reperfusion period,and to investigate the influence of fosinopril on action potential(AP),L-type calcium current(ICa-L) and ATP sensitive potassium current(I_K-ATP) in guinea pig ventricular myocytes undergone anoxia-reoxygenation Injury.METHODS AP,ICa-L and I_K-ATP in guinea pig ventricular myocytes undergone anoxia-reoxygenation injury were recorded using whole-cell current-clamp and patch-clamp techniques.RESULTS Anoxia-reoxygenation injury shortened action potential duration(APD50,APD90),the ICa-L peak of ventricular myocytes was decreased,the current-voltage(I-V) curve was shifted up,the activation curve was shifted right,the inactivation curve was shifted left,the membrane potential producing half-maximal activation(V_1/2) was increased and half-maximal inactivation(V_1/2) was decreased significantly.The normal closed ATP sensitive potassium channel opened fully ten minutes after reperfusion.When membrane potential was +80 mV,I_K-ATP density was(13.53±1.89)pA/pF.Compared with anoxia-reoxygenati on group,fosinopril precondition prolonged APD₅₀ and APD₉₀,increased the ICa-L peak of ventricular myocytes(P<0.01).At the same time,the I-V curve was moved up slightly,the activation curve was shifted left,the inactivation curve was shifted right,activation V_1/2 and inactivation V_1/2 approached to normal,ATP sensitive potassium channel was opened furtherly and the I_K-ATP was increased obviously.Compared with fosinopril precondition group,glibenclamide precondition had no effects above.CONCLUSION Fosinopril precondition can obviously improve the depressing state of L-type calcium channel injuried by anoxia-reoxygenation,and it also can accelerate the action potential parameter reversion of L-type calcium channel and reduce the effective refractory period dispersion and the formation of reentry activation.Fosinopril can protect the ventricular myocytes from reperfusion arrhythmia by its pharmacologic preconditioning which can open ATP sensitive potassium channel and increase corresponding current.