Anoctamin 1(ANO1) or TMEM16 A gene encodes a member of Ca^(2+) activated Cl^(-) channels(CaCCs) that are critical for physiological functions,such as epithelial secretion,smooth muscle contraction and sensory signal t...Anoctamin 1(ANO1) or TMEM16 A gene encodes a member of Ca^(2+) activated Cl^(-) channels(CaCCs) that are critical for physiological functions,such as epithelial secretion,smooth muscle contraction and sensory signal transduction.The attraction and interest in ANO1/TMEM16 A arise from a decade long investigations that abnormal expression or dysfunction of ANO1 is involved in many pathological phenotypes and diseases,including asthma,neuropathic pain,hypertension and cancer.However,the lack of specific modulators of ANO1 has impeded the efforts to validate ANO1 as a therapeutic target.This review focuses on the recent progress made in understanding of the pathophysiological functions of CaCC ANO1 and the current modulators used as pharmacological tools,hopefully illustrating a broad spectrum of ANO1 channelopathy and a path forward for this target validation.展开更多
基金supported by grants from the National Natural Science foundation of China (81573410)the Ministry of Science and Technology of China (2018ZX09711001-004-006)+2 种基金Shandong Provincial Medicine and Health Technology Development Plan (2019WS145, China)Medical Research Guidance Plan of Qingdao Municipal Health Committee (2019-WJZD091, China)Qingdao Excellent Young Medical Talent Training Project。
文摘Anoctamin 1(ANO1) or TMEM16 A gene encodes a member of Ca^(2+) activated Cl^(-) channels(CaCCs) that are critical for physiological functions,such as epithelial secretion,smooth muscle contraction and sensory signal transduction.The attraction and interest in ANO1/TMEM16 A arise from a decade long investigations that abnormal expression or dysfunction of ANO1 is involved in many pathological phenotypes and diseases,including asthma,neuropathic pain,hypertension and cancer.However,the lack of specific modulators of ANO1 has impeded the efforts to validate ANO1 as a therapeutic target.This review focuses on the recent progress made in understanding of the pathophysiological functions of CaCC ANO1 and the current modulators used as pharmacological tools,hopefully illustrating a broad spectrum of ANO1 channelopathy and a path forward for this target validation.