白藜芦醇对HERG钾通道电生理功能的影响

目的探讨白藜芦醇对稳定转染HERG基因的HEK293细胞上HERG钾通道的影响,进一步了解其抗心律失常的作用机制。方法传代得到单个HERG-HEK细胞,应用全细胞膜片钳技术记录HERG-HEK细胞上的HERG钾电流和动力学曲线(激活、失活、复活和去活化)。结果白藜芦醇(1、10、100μmol·L-1)浓度依赖性的抑制HERG步阶电流(IHERG)及其尾电流(IHERGtail),0mV电压下1μmol·L-1白藜芦醇抑制IHERG25.3%±9.4%,IHERGtail23.6%±11%;10μmol·L-1白藜芦醇抑制IHERG28%±8.4%,IHERGtail28.8%±9.1%;100μmol.L-1白藜芦醇抑制IHERG43.7%±1.5%,IHERGtail47.9%±11%(P<0.05,n=12)。100μmol·L-1白藜芦醇作用后失活时间常数减小,失活速率变快;去活化时间常数明显减小(P<0.05,n=12)。激活、瞬时失活和复活动力学没有明显变化。结论白藜芦醇通过影响通道的开放状态和失活状态抑制HERG钾电流,从而使得心肌细胞复极时间延长,改善快速性心律失常。

Effect of resveratrol on function of HERG K+ channels

Aim To investigated the effects of resveratrol on HERG currents(IHERG)resulting from human ether-a-go-go-related gene(HERG) expression in human embryonic kidney (HEK)(HERG-HEK)cells. Methods Enzyme digestion was performed to isolate single HERG-HEK cell and whole-cell patch-clamp technique was used to record HERG current and kinetic curves. Results Resveratrol inhibited HERG current in a concentration-dependent manner (1,10,100 μmol·L-1). The time constants of inactivation and deactivation were accelerated. Resveratrol did not change other channels kinetics (activation, on set of inactivation, recovery from inactivation). Conclusion Resveratrol inhibits the transfected HERG channels by influencing the open and inactivation state and it is the probable anti-arrhythmic mechanism.