MODULATION OF CARDIAC NAV CHANNEL FUNCTION AND ELECTROPHYSIOLOGY BY INTERACTING MOLECULES

通过相互作用分子调节心脏导航通道功能和电生理学

• 批准号: 9895841
• 负责人: JONATHAN R SILVA
• 金额: $ 38.13万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9895841
• 关键词: Action Potentials; Affect; Anti-Arrhythmia Agents; Arrhythmia; Binding; CRISPR/Cas technology; Cardiac; Cardiac Myocytes; Cell model; Cells; Complex; Computer Models; Data; Disease; Drug Interactions; Drug Kinetics; Electrophysiology (science); Epilepsy; Fluorometry; Goals; Heart; Human; Inherited; Intervention; Ion Channel; Kinetics; Knock-out; Learning; Link; Modeling; Molecular; Motion; Muscle Cells; Mutation; Myocardium; Organ; Pathology; Pharmaceutical Preparations; Pharmacology; Phenotype; Protein Isoforms; Proteins; Protocols documentation; Regulation; Research; Route; Shapes; Signal Transduction; Skeletal Muscle; Sudden Death; System; Testing; Therapeutic; Time; Tissue Model; Tissues; base; differential expression; improved; induced pluripotent stem cell; insight; kinetic model; novel; prevent; small molecule; voltage; voltage clamp

Abstract In excitable cells, voltage-gated Na+ channels initiate the action potential. In recent years, it has been discovered that these channels are composed of many parts to form a macromolecular signaling complex. These different parts precisely tune the function of Na+ channels to the cells that they reside in. This proposal aims to begin to discover mechanisms of how one component, the β-subunits, modulate the function and pharmacology of Na+ channels. If the proposed aims succeed, this new understanding could provide a route to more effective and precisely-directed therapies for excitability disorders such as arrhythmia and epilepsy.

摘要 在可兴奋细胞中，电压门控Na+通道启动动作电位。近年来，它已经 发现这些通道是由许多部分组成的，形成了一个大分子 信号复杂。这些不同的部分精确地调节细胞的Na+通道的功能 他们居住的地方。这项提议旨在开始发现一种 β亚基调节Na+通道的功能和药理。如果 提出的目标成功，这一新的理解可以提供一条途径，以更有效和 针对心律失常和癫痫等兴奋性障碍的精确定向治疗。