卡维地洛对HERG钾通道电生理功能及蛋白表达的影响  

Effect of carvedilol on HERG K^+ channels electric physiological function and protein expression

作　　者：史珊珊[1] 胡美钦[1] 戚志平[1] 佘柽柏[1] 刘冬敏[1] 李宝馨[1] 杨宝峰[1] 

机构地区：[1]哈尔滨医科大学药学院药理学教研室,黑龙江省生物医药重点实验室一省部共建国家重点实验室培育基地,黑龙江哈尔滨150081

出　　处：《中国药理学通报》2009年第6期737-742,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30572181)

摘　　要：目的探讨卡维地洛对稳定转染HERG基因的HEK(human embryonic kidney)293细胞上的HERG钾通道的影响。方法应用全细胞膜片钳技术记录在HEK293细胞上稳定表达的HERG钾通道的电流和动力学曲线(激活、失活、复活和去激活),研究不同浓度卡维地洛对HERG电流及动力学的影响;用Western blot技术定量的观察不同浓度卡维地洛对定位于HERG-HEK细胞膜上的HERG钾通道蛋白表达的影响。结果卡维地洛(10、100nmol.L-1,1、10μmol.L-1)浓度依赖性的抑制HERG步阶电流(Istep)及其尾电流(Itail)。由Hill方程得出IC50为539.6nmol.L-1,Hillslope为-0.64。1μmol.L-1卡维地洛作用后瞬时失活、去激活时间常数明显降低(P<0.05,n=10),而激活、失活、复活动力学无明显改变;Western blot检测结果显示卡维地洛组与无加药对照组HERG蛋白的表达无差别。结论卡维地洛通过影响通道的开放状态抑制HERG钾电流,加速瞬时失活和去激活动力学,对HERG蛋白的表达及成熟无影响。Aim To investigate the direct effects and mechanism of carvedilol on HERG channel stably expressing in human embryonic kidney-293 （ HEK293 ） cells. Methods Whole-cell patch-clamp technique was used to record HERG current and kinetic curves in single cells. Western blot methods were used to investigate the expression of HERG channel in different concentration of carvedilol. Result Carvedilol decreased HERG current in a concentration-dependent manner with an IC50 539.6 nmol.L^-1 , Hillslope -0. 64. The time constants of onset of inactivation and deactivation were accelerated. Other kinetcs （ activation, inactivation, recovery from inactivation ）had no significant changes. Based on western result, carvedilol had no effect on the generation and trafficking of HERG protein. Conclusion Carvedilol inhibits the transfected HERG channels by influencing the open state which is the probable anti-arrhythmie mechanism. There is no relationship between carvedilol and HERG channel expression.

关 键 词：卡维地洛 HERG钾通道 膜片钳技术 WESTERN BLOT 技术 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学] R329.25[医药卫生—基础医学]