Ca^(2+)激活Cl^-通道功能及分子基础研究进展  

Progress on Studies of Functions and Molecular Basis of the Ca^(2+)-activated Cl^- Channel

作　　者：王莉[1,2] 张海林[1] 

机构地区：[1]河北医科大学基础医学院药理学教研室,省部共建神经和血管生物学重点实验室,河北省新药药理毒理重点实验室,石家庄050017 [2]河北科技大学生物科学与工程学院,石家庄050018

出　　处：《中国细胞生物学学报》2012年第5期477-484,共8页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(No.30730031)资助项目~~

摘　　要：自从1983年Barish在爪蟾卵母细胞中发现钙激活的Cl–通道以来,此种类型Cl–通道一直在被广泛的研究,其在不同组织中的重要作用也被不断报道。但是,钙激活氯电流的分子机制一直未被阐明。直到2008年,由三个实验室分别发现了构成钙激活Cl–通道的分子基础为跨膜蛋白16A(transmembrane protein 16A,TMEM16A),这一发现使得人为通过基因手段调控钙激活Cl–通道的功能与表达成为可能。该文综述了钙激活Cl–通道在不同组织中的作用、TMEM16A的电生理和药理学特性以及TMEM16A在心肌肥厚和心衰中的可能作用,以及以Cl–通道作为药物作用靶点的研究进展。Calcium-activated chloride channels （CaCCs）, which play an important role in physiological functions, are gradually recognized since they were first described in the early 1980s by Barish in Xenopus oocytes. However, the molecular identification and pharmacology of CaCCs remained obscure. It was as late as 2008 that independent studies from three laboratories identified a gene encoding transmembrane protein 16A （TMEM16A） as the candidate for CACCs. This finding made it possible that CaCCs could be studied by genetic manipulation. This article reviews the progress on studies of CaCCs functions in different tissues, the electrophysiological and pharmacological properties of TMEM16A as potential drug target and their possible role during the process of arrhythmogenesis, myocardial hypertrophy and heart failure.

关 键 词：钙激活氯通道 跨膜蛋白16A 药理学 心肌肥厚 信号转导 

分 类 号：Q25[生物学—细胞生物学]