心脏肥厚性重构引起恶性室性心律失常的主要病理生理改变之一，是肌节和肌丝相关基因变异及蛋白数量和功能异常。肥厚型心肌病（HCM）的遗传机制分析一直是近年的研究重点。心肌肥厚致室速过程中，TNNI3 R186Q突变是否为致病基因尚未明确，IP3R是否受其调控及其机制均未知。我们的前期研究首次于中国家系中报导了R186Q突变, 前期预实验显示，成功构建R186Q突变小鼠，发现突变后小鼠心肌发生肥厚性改变并发生室速，且显示R186Q突变后cTnI表达增加, 通过降低IP3R泛素化水平稳定IP3R蛋白表达，但具体调控机制不明。本研究拟利用免疫共沉淀、共聚焦等技术，探寻 cTnI 是否通过调控IP3R 引起心肌细胞内钙负荷异常。并结合分子生物学及电生理技术，从体外水平探索cTnI 调控IP3R引起钙负荷异常导致心肌肥厚继而发生电生理紊乱的分子机制。

Aberrant sarcomere and filament-related genes is one of major pathophysiologies in remodeling of hypertrophic cardiomyopathy (HCM). The genetic mechanism of HCM，which has become a hot-point in the field of cardiovascular research. Until now, it is unknown whether the TNNI3 R186Q mutation is one of the cause of HCM, and unknown whether IP3R is modulated by cTnI in malignant ventricular arrhythmia-induced by myocardial hypertrophy. Our published data found R186Q mutation in a family line, and our preliminary data showed that myocardial hypertrophy and ventricular tachycardia happened in R186Q mutant mice, R186Q mutation increased the expression of cTnI, and stabilized the IP3R protein expression through reducing the ubiquitination level of IP3R. But the exact mechanism was unclear. This study will focus on the direct interaction between cTnI and IP3R by molecular analysis, and try to explore how cTnI modulates calcium level through IP3R in electrophysiological disorders by in vivo and in vitro experiments.