Transcriptional Regulation of KCNH2

摘要 昼夜节律有助于使心血管系统的最佳功能与心血管系统的每日变化相匹配 环境。正常的心血管节律为人们提供了生理优势。不幸的是， 正常的昼夜节律信号也可以揭示不良事件的时间模式，如心脏病发作，中风， 以及潜在心血管疾病患者的猝死。 现在出现的数据表明，不正常或不健康的日常节律会对正常生活产生负面影响 健康也是。例如，轮班工作反复导致内源性昼夜节律的变化，是一种 心血管疾病的独立危险因素。 在哺乳动物中，大脑中的视交叉上核(SCN)是主要的昼夜节律起搏器，有助于 将内生节律带到环境中。SCN节律通过光与环境同步， 它的信号有助于协调全身细胞的分子节奏。最新消息 这个应用是我们确定光周期的重复变化将如何影响分子昼夜节律信号。 心脏。 大多数细胞都有一个分子时钟信号机制，周期约为24小时。我们发现 心脏细胞(心肌细胞)分子时钟机制中的遗传干扰是主要原因 通过扰乱离子通道功能的调节而引起的心脏电生理的异常改变。 这项应用的目标是确定光周期中的重复变化如何影响分子时钟 小鼠心脏中的信号及其对离子通道功能的调节。 目的1.确定心脏分子钟调节不同离子通道的新机制。 目的2.确定光的重复变化如何影响心脏和离子的分子时钟信号 航道整治。 这个项目在时间生物学和心脏电生理学之间创造了新的知识。

Summary Circadian rhythms help to match the optimal function of the cardiovascular system to the daily changes in the environment. Normal cardiovascular rhythms provide a physiological advantage to people. Unfortunately, normal circadian signaling can also unmask a time-of-day pattern in adverse events like heart attack, stroke, and sudden death in patients with underlying cardiovascular disease. Emerging data now show that abnormal or unhealthy daily rhythms can create a negative impact on normal health too. For example shiftwork, which repeatedly causes shifts in endogenous circadian rhythms, is an independent risk factor for cardiovascular disease. In mammals the suprachiasmatic nucleus (SCN) in the brain is the primary circadian pacemaker that helps to entrain endogenous rhythms to the environment. SCN rhythms are synchronized to the environment via light, and its signaling helps to coordinate the molecular rhythms in cells throughout the body. What is new about this application is we determine how repeated changes in light cycle will impact molecular circadian signaling in the heart. Most cells have a molecular clock signaling mechanism that cycles with a periodicity of ~24 hours. We found genetic disruptions in the molecular clock mechanism of heart cells (cardiomyocytes) primarily causes abnormal changes in cardiac electrophysiology by disrupting the regulation of ion channel function. The goal of this application is to determine how repeated shifts in the light cycle impact molecular clock signaling in the mouse heart and its regulation on ion channel function. Aim 1. To identify new mechanisms with which the cardiac molecular clock regulates different ion channels. Aim 2. To determine how repeated changes in light impact molecular clock signaling in the heart and ion channel regulation. This project creates new knowledge at the interface between chronobiology and cardiac electrophysiology.