MOLECULAR PHYSIOLOGY OF CARDIAC POTASSIUM CHANNELS

心脏钾通道的分子生理学

• 批准号: 2028425
• 负责人: CAROL A VANDENBERG
• 金额: $ 19.66万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2028425
• 关键词: Xenopus; Xenopus oocyte; action potentials; cardiovascular pharmacology; electrical conductance; gene deletion mutation; guinea pigs; heart cell; immunocytochemistry; laboratory rabbit; laboratory rat; magnesium; plasmids; polyamines; potassium channel; protein biosynthesis; protein structure function; resting potentials; site directed mutagenesis

The goal of this project is an understanding of the molecular basis of the structure and function of inwardly rectifying potassium channels. These channels are central to the functioning of cardiac cells where they are involved in controlling the action potential waveform, duration, resting potential and controlling cell excitability. This proposal concentrates on the inward rectifier channels of the K1 class that show strong asymmetry in potassium conductance and are found prominently in heart and brain. The goal of this project is to use an integrated molecular, biophysical and biochemical approach to investigate a) the functional permeation, conduction and rectification properties of K1 channels, b) the channel polypeptide transmembrane topology, and c) the subunit composition and assembly of inward rectifier channels. The specific aims of the project are: Aim 1. The functional characteristics of the channels will be investigated to ascertain the molecular basis for channel pore properties, channel permeation and block, and channel rectification. Aim 2. The structure of the channel polypeptide across the cell membrane will be determined. Aim 3. The subunit composition of the channels will be elucidated, and the domains responsible for channel assembly will be ascertained. The results of these studies will provide new information about the molecular mechanisms involved in the function of the inward rectifier channels in the heart and brain. An understanding of the molecular architecture and function of the K1 channels will enable the development of K1 channel therapeutic agents to treat cardiovascular and neuronal disease.

该项目的目标是了解 内向整流钾通道的结构和功能。 这些通道对于心肌细胞的功能至关重要 参与控制动作电位波形、持续时间、 静息电位和控制细胞兴奋性。 该提案集中于 K1 的内向整流器通道 钾电导表现出强烈不对称性的一类并被发现 主要分布于心脏和大脑。该项目的目标是使用 综合分子、生物物理和生化方法进行研究 a) 功能性渗透、传导和整流特性 K1 通道，b) 通道多肽跨膜拓扑​​结构，以及 c) 内向整流器通道的子单元组成和组装。 该项目的具体目标是： 目标 1. 渠道的功能特征是 研究以确定通道孔的分子基础 性质、通道渗透和阻塞以及通道整流。 目标 2. 跨细胞膜通道多肽的结构 将被确定。 目标 3. 将阐明通道的亚基组成，并且 负责通道组装的域将被确定。 这些研究的结果将提供有关 内向整流器功能涉及的分子机制 心脏和大脑中的通道。对分子的理解 K1通道的架构和功能将促进发展 K1通道治疗剂治疗心血管和神经元 疾病。