MOLECULAR PHYSIOLOGY OF CARDIAC POTASSIUM CHANNELS

这个项目的目标是了解分子基础 内向整流钾通道的结构和功能。 这些通道是心脏细胞功能的中心，在那里它们 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。 这项建议集中在K1的内向整流通道 在钾电导上表现出强烈不对称性的类别，并发现 突出表现在心脏和大脑上。此项目的目标是使用一个 综合分子、生物物理和生化方法研究 A)功能渗透、传导和整流性能 K1通道，b)通道多肽跨膜拓扑，以及c) 内向整流通道的子单元组成和组装。 该项目的具体目标是： 目标1.渠道的功能特征将是 探讨孔道孔隙形成的分子基础 性质、渠道渗透和堵塞，以及渠道整治。 目的2.跨细胞膜通道多肽的结构 将会被确定。 目的3.阐明通道的亚基组成，并 负责通道组装的域将被确定。 这些研究的结果将提供有关 内向整流作用的分子机制 心脏和大脑中的经络。对分子的理解 K1频道的架构和功能将使开发成为可能 治疗心血管和神经元疾病的K1通道治疗剂 疾病。

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.