牛磺酸镁对哇巴因致大鼠心室肌细胞瞬时外向钾离子通道异常的影响

Effect of taurine-magnesium coordination compound on abnormality of transient outward potassium channel induced by ouabain in rat cardiomyocytes

目的:观察牛磺酸镁配合物(taurine magnesium coordination compound,TMCC)在细胞水平对哇巴因致大鼠心室肌细胞心律失常的瞬时外向钾电流的作用。方法:酶解法分离大鼠单个心室肌细胞,5μmol·L-1哇巴因诱发细胞水平心律失常,采用全细胞膜片钳技术,在电压钳模式下记录下不同浓度TMCC及胺碘酮对正常细胞和哇巴因所致大鼠单个心室肌细胞心律失常模型I to变化。结果:TMCC对正常细胞I to呈浓度依赖性抑制作用。24μmol·L-1胺碘酮使电流减少到(17.36±1.20)pA/pF(P<0.01)。TMCC及胺碘酮均使激活曲线右移,失活曲线左移。5μmol·L-1哇巴因使I to从(25.74±3.60)pA/pF减少到(18.79±2.78)pA/pF(P<0.01)。哇巴因使激活曲线右移,失活曲线左移。TMCC未能进一步改变哇巴因诱导I to的减少,而胺碘酮则使之减小到(13.64±1.03)pA/pF。TMCC对激活、失活曲线无明显作用,而胺碘酮可使激活曲线进一步右移,失活曲线进一步左移。结论:TMCC抑制大鼠正常心室肌细胞的I to,I to是TMCC抗心律失常作用的离子靶点之一,TMCC不会进一步抑制由哇巴因诱发I to的减少。

Objective： To investigate the effect of taurine magnesium coordination compound （TMCC） on transient outward potassium current （Ito） in rat cardiomyocytes without or with oubain-induced arrhythmia. Meth- ods： Single rat cardiomyocytes were isolated by means of enzymatic dissociation. Whole-cell patch clamp was used to record It. in normal cardiomyocytes and the single rat ventricular cardiomyoeytes with ouabain-induced arrhythmi- a. Results： In normal ventricular cardiomyocytes, I,o was blocked by 100 -400 umol L- TMCC in a concentra- tion-dependent manner. I,o （pA/pF） was decreased from （25.74 ± 3.60） to （ 18.79 ±2.78） by 5 umol. L-1 oua- bain, and to （17.36 ± 1.20） by 24 txmol. L-t amiodarone. Ouabain shifted the steady-state activation curves to the right, and the steady-state inactivation curves to the left. TMCC failed to further inhibit abnormal transient outward potassium currents induced by ouabain, and had no effect on the steady-state activation and inactivation curves; however, amiodarone further inhibited the abnormal currents, and further shifted the steady-state activation and in- activation curves. Conclusion ： TMCC inhibits 14o, which is one of ion targets of antiarrhythmic effect of TMCC, but cannot further inhibit ouabain-decreased Ito.