钾离子通道蛋白Shaker对果蝇心脏衰老的保护作用

钾离子通道在心肌细胞动作电位复极过程中起着重要作用。钾离子通道蛋白种类繁多,已知钾离子通道蛋白KCNQ和HERG/eag参与心脏动作电位的形成,调节心脏收缩节律。钾离子通道蛋白Shaker是果蝇(Drosophila)体内发现的第一个电压门控钾离子通道,维持神经元和肌肉细胞的电兴奋性,但是目前其在成人心脏功能中的作用仍不清楚。本研究以果蝇为模型,高频电刺激模拟心脏应激状态,观察钾离子通道蛋白shaker基因突变体的心衰发生率。同时,利用心脏特异性启动子hand4.2Gal4特异性敲低钾离子通道蛋白Shaker的表达;果蝇成体心脏生理学功能分析系统分析了1、3、5周龄特异性敲低钾离子通道蛋白Shaker的心脏表型。结果表明,shaker基因突变将严重影响果蝇心脏抗应激能力,表现在高频电刺激后的心力衰竭发生率显著性升高;心脏特异性敲低shaker基因导致5周龄果蝇心律失常发生率显著性增加;心脏特异性敲低HDAC3将显著降低果蝇寿命。综上所述,本研究推测钾离子通道蛋白Shaker在衰老过程中维护果蝇正常的心脏功能。

Potassium channel Shaker play a protective role against cardiac aging in Drosophila

Potassium channels,which are the most diverse group of the ion channel family,play an important role in the repolarization of cardiomyocytes.Recent studies showed that potassium channels,such as KCNQ and HERG/eag,play an important role in regulating adult heart function through shaping the action potential and maintaining the rhythm of cardiac contraction.The potassium channel protein Shaker is the first voltage-gated potassium channel found in Drosophila to maintain the electrical excitability of neurons and muscle cells,but its role in adult cardiac function is still unclear.In this study,Drosophila was used as a model to study the role of Shaker channel in the maintenance of cardiac function under stress and aging.The incidence of heart failure was observed in shaker mutant after external electrical pacing,which simulates cardiac stress.Additionally,The cardiac-specific driver hand4.2 Gal4 was used to specifically knock down the expression of the potassium channel shaker in Drosophila.The cardiac parameter was analyzed at 1,3,5 weeks of age on cardiac specific knockdown of shaker using Drosophila adult cardiac physiological assay.The results showed that the mutation of shaker gene seriously affect the cardiac function under stress,demonstrated by significant increase in heart failure rate under electrical stimulation.In addition,cardiac specific knockdown of shaker increased the incidence of arrhythmias in Drosophila at the age of 5 weeks.Cardiac-specific knockdown of shaker reduces life span.Therefore,the results of this study suggest a vital role of the potassium channel shaker in maintaining normal cardiac function during aging.