缺血-再灌注对心肌细胞钠快通道电流的影响

Effects of ischemia-reperfusion on sodium channel of myocytes

目的:探讨在心肌缺血-再灌注后钠快通道电流的变化及其在室性心律失常发生中的作用。方法:以常规方法制备大鼠心肌缺血-再灌注模型,以酶解法分离单个心室肌细胞,采用全细胞膜片钳记录技术观察缺血10和30 min后再灌注组(10 min和30 min组)的心室肌细胞钠快通道电流(INa)的变化,以正常心肌INa为对照,同时设假手术对照组。结果:缺血10 min再灌注组INa受到抑制,电流密度-电压关系曲线上移,而缺血30 min再灌注组增大,电流密度-电压关系曲线下移,峰值钠电流密度对照组为(-13.55±4.32)pA/pF(n=10个细胞),缺血10 min和30 min再灌注组分别为(-6.51±2.45)pA/pF(n=10个细胞)和(-41.27±9.68)pA/pF(n=10个细胞),与对照组相比,差异均有极显著性意义(P<0.001);缺血10 min再灌注失活曲线左移,而缺血30 min再灌注组又右移,半数最大失活电位对照组为(-105±12)mV(n=10个细胞),缺血10 min和30 min再灌注组分别为(-112±16)mV(n=10个细胞)和(-101±12)mV(n=10个细细胞),与对照组比较,缺血10 min再灌注组显著减小(P<0.001),而缺血30 min再灌注组变化不明显(P>0.05)。结论:缺血10 min再灌注组心室肌细胞钠快通道受抑制,而缺血30 min再灌注组心室肌细胞钠快通道反而激活,可能为缺血-再灌注性心律失常发生的机制之一。

Objective ：To study the changes of sodium currents （INa） of rat reinfuse myocytes after acute myocardial ischemia. Methods：An ischemia-reperfused model was made by routine method. Single ventricular myocytes were isolated enzymatically from rat hearts reperfused 10 and 30 minute＇ s after myocardial ischemia, and INa was recorded by using patch clamp techniques in the whole cell configuration. Results ：The peak of INa from the cells in the 10 min group was significantly reduced （ -6.51± 2.45 ） pA/pF, （n=10）, compared with the cells from the control group （ -13.55 ±4.32） pA/pF, （n = 10） , P 〈 0. 001, while the peak of INa from the cells in the 30 min group was significantly increased （ -41.27±9.68） pA/pF （n = 10）. The steady-state inactivation curve was shifted in the hyperpolarizing direction in the 10 min group and in the depolarizing direction in the 30 min group, the half-maxi- mal voltage dependence of inactivation（V1/2） was （ -112±16）mV in the 10 min group, （ -101 ± 12） mV in the 30 min group , and （ - 105±12）mV in the control group. Conclusion：Inhibitation of INa was found in the reperfused 10 minute＇ s after ischemia and activation was noted in those 30 minute＇ s after it, which might be one of the mechanisms underlying the development of ventricular arrhythmia related to reinfusion after myocardial ischemia.