心肌Ito钾通道中硫化氢（H2S）分子开关的定位及其功能研究

项目名称： 心肌Ito钾通道中硫化氢（H2S）分子开关的定位及其功能研究

项目编号： No.31471088

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 朱依纯

作者单位： 复旦大学

项目金额： 92万元

中文摘要： 在前期工作和预实验已明确H2S直接作用与Ito钾通道孔形成亚单位Kcnd2以及二硫键是H2S调控其靶分子结构和功能的分子开关的基础上，结合基因重组技术和电生理技术，研究H2S调控Ito钾通道的分子开关机制及其生理意义，包括确定Kcnd2中二硫键的确切位置及其功能，以及H2S是否将其作为分子开关调控Ito钾通道的结构和功能；还包括研究H2S通过调控Ito钾通道对心肌细胞动作电位时程、绝对不应期以及急性心肌缺血时严重室性心律失常的作用。研究工作的意义不但有助于揭示H2S调控心脏离子通道结构和功能的机制，还有助于探索治疗心性心肌梗死所致严重心律失常的新方法。

中文关键词： 硫化氢；Ito钾通道；分子开关；心律失常；心肌细胞

英文摘要： Our previous work and pilot studies have clarified that H2S directly targets at the pore-forming subunit of Ito potassium channels, the Kcnd2 subunit. And the disulfide bond serves as a molecular switch for H2S to regulate the structure and function of the Ito potassium channels. Using recombinant DNA technology combined with electrophysiological technology, the present project aims to investigate the mechanisms underlying the regulation of H2S on the Ito potassium channels and the physiological role of this effect. This includes identification of disulfide bonds contained in Kcnd2 and clarification of the function of this bridge bond. We will also investigate if H2S regulates the structure and function of the Ito potassium channels via this molecular switch. The physiological role of this H2S effect on action potential, absolute refractory period, and severe ventricular arrhythmia induced by acute ischemia will also be examined. The study not only helps to clarify the mechanisms underlying H2S-induced regulation on ion channels and to develop new approaches for the treatment of severe ventricular arrhythmia induced by acute myocardial infarction.

英文关键词： Hydrogen sulfide;Ito potassium channels;Molecular switch;Arrhythmia;Cardiomyocytes