癫痫是一种反复发作的慢性脑功能失调综合征, 患者死亡率远高于健康人群，其中癫痫猝死是最常见的死因之一。我们前期研究发现在SENP2敲除小鼠中，Kv7.2/Kv7.3钾离子通道蛋白的SUMO修饰增加，引起神经元M电流显著减小，诱发癫痫和心脏房室传导阻滞，最终导致癫痫猝死。但是SUMO修饰调控Kv7.2/Kv7.3通道活性及M电流导致癫痫猝死的具体机制仍不清楚。本课题拟利用细胞和SENP2敲除小鼠模型系统研究SUMO修饰调控Kv7.2/Kv7.3及其介导的M电流的分子机制，分析迷走神经中Kv7.2/Kv7.3通道蛋白的过度SUMO修饰在其介导的房室传导阻滞和心脏停搏中的作用，并探讨阿托品或瑞替加滨长期给药阻止SENP2缺失所致癫痫猝死的可行性。本项目的完成将揭示SUMO修饰异常引起癫痫猝死的重要分子机制，为癫痫猝死疾病的临床治疗提供新的理论基础和潜在的靶向治疗位点。

Epilepsy is a recurrent chronic brain disease, the mortality rate is much higher in epileptic patients than in healthy population, and sudden unexpected death in epilepsy (SUDEP) is one of the most common cause of death in patients with epilepsy. Our previous study identified that the hyper-SUMOylation of potassium channel protein Kv7.2/Kv7.3 caused by SENP2 deficiency affects the channel activity, reduced M-current, induced epilepsy and atrioventricular block and SUDEP in SENP2 knockout mice, however, the underlying molecular mechanism is still unclear. This project proposes to use cell lines as well as SENP2 knockout mice to study the mechanisms of SUMOylation on Kv7.2/Kv7.3 to regulate M-current, find out the role of hyper-SUMOylation of Kv7.2/Kv7.3 in vagus nerve during epilepsy and induced atrioventricular block and cardiac arrest, and explore the potential prevention role of atropine or retigabine in SUDEP caused by SENP2 deficiency. This project may reveal the molecular mechanisms of SUMOylation in regulation of Kv7.2/Kv7.3 and M-current, and provide a theoretical basis and potential target site for the clinical treatment of SUDEP.