PDZ Interaction and Inward Rectifier K+ Channel Function

描述(由申请人提供)： 强烈的内向整流钾通道参与动作电位。 复极化、细胞兴奋性的调节和细胞的测定 大脑和其他可兴奋细胞的静息电位。事实上，基因突变 这些通道与细胞兴奋性缺陷有关，周期性的 瘫痪、心律失常和发育异常。最近，它 已经证明，与离子通道相关的蛋白质可能 调制通道的功能属性，并且这种相互作用可以 对正常的生理和疾病有深远的影响。中的缺陷 与通道相互作用的蛋白质可能导致通道表达的问题， 膜靶向，通道与信号复合体的关联，以及 通道电活动。 这项提议旨在识别和表征与之相互作用的蛋白质。 内向整流钾通道。最近，我们发现了这样一种 内向整流通道与支架蛋白SAP97的相互作用 在大脑里。这个项目的目标是识别蛋白质的复合体。 与内向整流钾通道相关，并分析 这些蛋白质聚集、定位和调节的功能能力 通道的活跃性。

DESCRIPTION (provided by applicant): The strong inward rectifier potassium channels are involved in action potential repolarization, modulation of cell excitability, and determination of cell resting potential in the brain and other excitable cells. Indeed, mutations in these channels are associated with defects in cell excitability, periodic paralysis, cardiac arrhythmias, and developmental abnormalities. Recently, it has been demonstrated that proteins that are associated with ion channels may modulate the functional properties of the channels, and such interactions may have profound implications in normal physiology and disease. Defects in channel-interacting proteins could lead to problems in channel expression, membrane targeting, association of channels with signaling complexes, and channel electrical activity. This proposal aims to identify and characterize the proteins that interact with inward rectifier potassium channels. Recently, we have identified such an interaction between inward rectifier channels and the scaffolding protein SAP97 in the brain. The goal of this project is to identify the complex of proteins that associate with inward rectifier potassium channels and to analyze the functional ability of these proteins to cluster, localize and regulate the activity of the channels.