钙激活氯通道（CaCC）在多种生理功能中起着重要作用。近年来，许多器官组织的CaCC通道已被确认为ANO1的基因产物，但是心脏CaCC通道的代表基因迄今未明。由于心肌CaCC通道不仅参与细胞正常的电活动，其功能异常还可引发心律失常，因此明确心脏CaCC通道的分子构成一直是倍受学术界关注的课题。我们最近的研究发现：小鼠心肌组织有ANO1 mRNA 和蛋白水平的表达，推测ANO1蛋白很可能是心肌内源性CaCC通道的代表蛋白。本项目拟以原代培养的ANO1基因敲除或ANO1 mRNA静默的小鼠心肌细胞为模型，以细胞CaCC通道电流的减弱或消失为判断指标（全细胞膜片钳法）, 评判ANO1蛋白是否参与心肌CaCC通道的组成。在此基础上，进一步观察ANO1在心脏各部位的分布和 ANO1对离体心肌细胞电活动及整体动物心率的影响，并研究ANO1通道的调控机制，从而为治疗相关的心律失常提供新的治疗靶点。

Ca-activated Cl channels (CaCC) play important roles in many physiological functions. Recently, CaCC channels have been identified to be the genetic products of Anoctamin 1 (ANO1) in many organs. However, the representative gene for the CaCC channel in heart has not been clear as yet. Since cardiac CaCC channels not only participate in the normal electric activity but also its abnormal function causes cardiac arrhythmia, it has been a subject with close attention all the time in the field to identify the representative gene of the cardiac channel. Our recent study has found that there is expression of ANO1 in the mouse cardiac tissue at levels of mRNA and protein. Therefore, we presume that ANO1 is probably the representative protein of the cardiac endogenous CaCC channels. In the project, as cell models, we will use primarily cultured murine cardiomyocytes with ANO1 gene knocked out or with ANO1 mRNA knocked down via RNA interference approach. We will evaluate whether ANO1 constitutes the cardiac CaCC channels using weakening or disappearance of CaCC currents from the cardiomyocytes (tested with whole-cell patch clamp) as a judging parameter. Based on the evaluation, we will further observe the distribution of ANO1 in all parts of the heart and the effect of ANO1 on the electric activity of isolated cardiomyocytes and on the heart beating of the whole animal. We will also study the regulatory mechanism of the ANO1 channels. The project aims to provide a new therapeutic target for the relevant arrhythmia.