TMEM16A通道结构、功能与药物靶点  

TMEM16A channel:structure,(patho)physiological function and drug target

作　　者：安海龙[1,2,3] 史赛 庞春丽 陈娅斐 郭帅 纪秋爽[3] 展永 AN Hailong;SHI Sai;PANG Chunli;CHEN Yafei;GUO Shuai;JI Qiushuang;ZHAN Yong(State Key Laboratory of Reliability and Intelligence of Electrical Equipment,Hebei University of Technology,Tianjin 300401,China;Key Laboratory of Electromagnetic Field and Electrical Apparatus Reliability of Hebei Province,Hebei University of Technology,Tianjin 300401,China;Key Laboratory of Molecular Biophysics of Hebei Province,School of Science,Hebei University of Technology,Tianjin 300401,China)

机构地区：[1]河北工业大学省部共建电工装备可靠性与智能化国家重点实验室,天津300401 [2]河北工业大学河北省电磁场与电器可靠性重点实验室,天津300401 [3]河北工业大学理学院河北省分子生物物理重点实验室,天津300401

出　　处：《河北工业大学学报》2020年第5期35-44,共10页Journal of Hebei University of Technology

基　　金：河北省自然科学基金(C2018202302);国家自然科学基金(11735006,81830061,31600594)。

摘　　要：TMEM16A(也称ANO1)是钙激活氯离子电流(CaCCs)的分子基础。研究表明,TMEM16A参与调节卵母细胞的受精、气道和外分泌腺分泌、嗅觉和感觉信号的传导、平滑肌的收缩以及心脏细胞的兴奋。TMEM16A的功能障碍或表达异常与多种疾病的发生发展有关,包括胃肠道功能障碍、神经性疼痛和多种癌症。本文综述了本课题组和其他课题组对TMEM16A通道的研究进展,主要聚焦于TMEM16A通道的结构和功能,TMEM16A通道的生理、病理功能及以该通道作为靶点的药物发现。最终讨论了TMEM16A药理调节剂可能的药理作用方案。TMEM16A的结构和相关疾病的知识将对TMEM16A调节剂药物的发现和应用产生积极影响。TMEM16A(also known as anoctamin 1,ANO1)is the molecular basis of the calcium-activated chloride chan⁃nels(CaCCs).Studies have shown that TMEM16A is involved in regulating fertilization of oocytes,transport of matter across cell membranes,transduction of olfactory and sensory signals,contraction of smooth muscle,and excitement of heart cells.The dysfunction or aberrant expression of TMEM16A is associated with the development of various diseases including gastrointestinal motility disorders neuropathic pain and various cancers.The article reviews the research prog⁃ress of the TMEM16A channel of our research group and other groups,focusing on the structure and function of the TMEM16A channel,(patho)physiological function and drug discovery using this channel as target.Finally,the scheme of possible pharmacological effects of TMEM16A pharmacological modulators were discussed.Understanding well the structure and related diseases of TMEM16A will have a positive impact on the discovery and application of TMEM16A modulator drugs.

关 键 词：离子通道 TMEM16A/CaCCs 结构 功能 药物靶标 

分 类 号：Q6-3[生物学—生物物理学]