人类果蝇相关基因钾通道调控因素与作用药物研究进展

Biosynthesis regulation and drug development for human ether-a-go-go related gene potassium channel:research advances

人类果蝇相关基因(hERG)编码快速延迟整流钾离子通道(Ikr)的α亚基,在Ⅲ期动作电位复极过程中起着重要的作用。影响hERG通道功能的因素有很多,药物抑制或者其他因素(如低钾等)都会使hERG功能发生障碍或改变表达。而hERG通道的这些变化常会引起心脏QT间期延长,诱发尖端扭转型室性心动过速,甚至导致心源性猝死。由于hERG通道是抗心律失常药物的重要靶点,并且在药物安全性评价过程中发挥重要作用。因此,hERG钾通道对于指导新药开发,实现针对hERG钾通道的抗心律失常治疗具有深远的意义。本文主要阐述了hERG通道的结构与功能,调节通道合成表达的因素、hERG通道异常与QT延长综合征的关系、拯救hERG通道表达异常的策略,为hERG通道的深入研究提供一定的参考和依据。

Human ether-a-go-go related gene （hERG） encodes α subunit of Ikr potassium channel which plays an essential role in Ⅲ phase repolarization of action potential. The expression and/or function of hERG channel could be influenced by mang factors, such as diverse drugs,low temperature or low K ＋ , which may cause the QT interval prolongation, torsade de points and even sudden cardiac death. Therefore, the research of hERG potassium channel has significance for guiding development of new drugs and individu- alized treatment of arrhythmia. The hERG potassium channels as anti-arrhythmic drug treatment target which plays an important roles in new drugs safety test and development. This review summarizes recent progresses of structure and functions of hERG channel, the bio- synthesis process of bERG potassium channel and regulatory elements, relationship between hERG potassium channel and long QT syn- drome, and treatment for abnormal expression of hERG channel, which provides reference and basis for in-depth study of bERG chan- nel.