特发性房颤的病因未明,其多为阳离子通道蛋白突变所致。TRPM4是钙离子激活的阳离子通道蛋白,申请者首次发现TRPM4蛋白在牛心脏浦肯野氏纤维中高表达并证明TRPM4突变可引起心脏传导阻滞和Brugada综合症。因此我们推测TRPM4的突变可引起特发性房颤。预实验在51位特发性房颤患者中发现2个杂合的TRPM4错义突变：c.2531 G>A;p.G844D和c.2680 G>A;p.V894I。为进一步证实TRPM4与特发性房颤的相关性，拟(1) 检测TRPM4蛋白在牛，大小鼠和人类心脏传导系统的系统表达，为揭示TRPM4在心脏传导阻滞，Brugada综合征和特发性房颤中的作用提供证据；(2)收集约250位特发性房颤患者的血液（51位已完成），提取DNA，通过高分辨率溶解曲线和/或测序的方法，检测TRPM4的突变并对突变进行电生理研究，探索特发性房颤的发病机制。

Idiopathic atrial fibrillation is usually caused by mutations of the cation channel proteins.TRPM4 is a Ca2+-activated nonselective cation channel. We have for the first time found high expression of TRPM4 in bovine cardiac Purkinje fibers and shown that Isolated cardiac conduction block and Brugada Syndrome are caused by the mutation of TRPM4. We speculate that TRPM4 mutations can cause idiopathic atrial fibrillation. In our preliminary experiment we found 2 heterozygous TRPM4 missense mutation in 51 patients with idiopathic atrial fibrillation.In order to further prove the correlations of TRPM4 in idiopathic atrial fibrillation, following two steps will be carried out in this experiment:(1)The expression of TRPM4 in rat，mouse and human cardiac conduction system will be detected to clarify TRPM4 expression in the direct pathology of Cardiac conduction block，Brugada Syndrome and Idiopathic atrial fibrillation. (2) High Resolution Melting curve and/or DNA sequencing will be carried out, following DNA extraction from blood of 250 patients（51 patients have been done） with Idiopathic atrial fibrillation to confirm the correlation of mutation of TRPM4 and Idiopathic atrial fibrillation . Electrophysiological study will be done on the mutations, to explore the pathogenesis of idiopathic paroxysmal atrial fibrillation.