哇巴因诱发大鼠心律失常作用靶点的研究

Study of ion targets in Ouabain-induced rat arrhythmia

目的 观察哇巴因对大鼠心室肌细胞动作电位时程、钾通道的作用 ,探讨哇巴因诱发心律失常的作用机制 ,为寻找新的抗心律失常药物提供依据。方法 应用全细胞膜片钳技术记录哇巴因对大鼠心肌细胞动作电位时程 (APD)、内向整流钾电流 (Ik1 )、瞬时外向钾电流 (Ito)的作用。结果 ①哇巴因 5μmol/L使大鼠心室肌细胞动作电位时程从给药前的 86 .3ms± 2 5 .2ms(APD90 ) ,缩短至 58.9ms± 2 0 .8ms(n =5 ,P <0 .0 1 ,给药 1 0min) ;②哇巴因 5μmol/L可增加大鼠心室肌细胞内向整流钾电流 ,使Ik1 从 - 1 868pA± 1 88pA增加到 - 2 393pA± 367pA(刺激电压 - 1 2 0mV ,n=1 0 ,P <0 .0 1 ) ;③哇巴因 5μmol/L可增加大鼠心室肌细胞瞬时外向钾电流 ,使Ito从 1 2 73pA± 31 8pA增加到 1 70 7pA± 486pA(刺激电压 +60mV ,n =5 ,P <0 .0 1 )。结论 哇巴因诱发室性心律失常可能与它缩短心室肌细胞动作电位时程有关 ,而Ito的增加使二期平台期缩短 ,Ik1 的增加使三期复极加快 ,均参与了动作电位时程缩短的过程。同时增加Ik1 将影响静息膜电位 。

Objective To observe the effects of Ouabain on action potential duration(APD),potassium channels in rat ventricular myocytes and to discuss the ionic mechanism of arrhythmia induced by Ouabain. Methods Using whole cell patch clamp technique to record the effects of Ouabain on APD and inward rectifier potassium current(I k1 ), transient outward potassium current(I to ) in rat ventricular myocytes. Results ①Ouabain 5μmol/L shortened the APD of rat ventricular myocytes, APD 90 (90% repolarization) from 86.3ms±25.2ms to 58.9ms±20.8ms( n =5, P <0.01,10min after administration);②Ouabain 5μmol/L increased I k1 significantly from -1868pA±188pA to -2393pA±367pA at -120mV ( n =10, P <0.01);③Ouabain 5μmol/L increased I to from 1273pA±318pA to 1707pA±486pA at +60mV( n =5, P <0.01).Conclusion One of the arrhythmogenesis mechanisms of Ouabain is due to the decrease of APD in the heart, and the increases of I k1 and I to can explain this phenomenon. At the same time, the increase of I k1 will affect the resting potential, which may increase the sensitivity of membrane.