心力衰竭心肌细胞电重构及离子通道异常活动，复极离散度增大，导致恶性心律失常。KATP通道开放促进膜复极，降低胞内钙超载，但心力衰竭时KATP通道功能受损，其机制尚不清楚。我们前期研究表明，心肌AKAP蛋白与KATP相互联系，整合MuRF1和Bin1之间信号传导，促膜复极化，阻止细胞内钙超载。本项目组提出如下科学假说：AKAP介导MuRF1/BIN1信号对心力衰竭心肌细胞KATP通道的损伤作用。拟采用膜片钳、胞内钙测定、分子生物学等技术，研究AKAP介导MuRF1/BIN1信号通路功能及其对心力衰竭心肌细胞KATP通道及细胞电重构损伤调节机制。研究结果将更好地认识MuRF1/BIN1信号通路对KATP通道的调节作用及心力衰竭恶性心律失常的分子机制，对指导筛选心力衰竭恶性心律失常治疗的新靶点具有重要的理论意义和实用价值。

Electrical remodeling and abnormal ionic channels activity increase the dispersion of repolarization, and lead to the occurrence of malignant arrhythmia. The open of KATP channels (ATP-sensitive potassium channels) contribute to the membrane repolarization, and decrease intracellular calcium overload in cardiomyocytes. There is little knowledge on intracellular calcium overload and dysfunctional mechanisms of KATP channels in heart failure. Our preliminary data have shown that KATP channel coupled by AKAP-mediated MuRF1/Bin1 signaling transduction in cardiomyocytes accelerated membrane repolarization and prevented intracellular calcium overload. The project team proposes the following scientific hypotheses: impairment of cardiac KATP channels by AKAP mediated MuRF1/Bin1 signaling pathway. To investigate the function of AKAP-mediated MuRF1/BIN1 signaling pathway and its regulation mechanism on KATP channel and cell electrical remodeling damage in cardiac myocytes with heart failure, we combined multi-techniques such as whole-cell and single channel patch clamp techniques, molecular biology approaches and calcium transient. These results will better understand the regulatory role of MuRF1/BIN1 signaling pathway on cardiac KATP channels and the molecular mechanism of malignant arrhythmias in heart failure, which has important theoretical significance and practical value in guiding the screening of new targets for malignant arrhythmias in heart failure.