PDZ Interaction and Inward Rectifier K+ Channel Function

描述（由申请人提供）： 强内向整流钾通道参与动作电位 复极化、细胞兴奋性的调节以及细胞的测定 大脑和其他可兴奋细胞的静息电位。事实上，突变 这些通道与细胞兴奋性、周期性缺陷有关 瘫痪、心律失常和发育异常。最近，它 已证明与离子通道相关的蛋白质可能 调节通道的功能特性，这种相互作用可能 对正常生理和疾病具有深远的影响。缺陷于 通道相互作用蛋白可能会导致通道表达问题， 膜靶向、通道与信号复合物的关联，以及 通道电活动。 该提案旨在识别和表征与相互作用的蛋白质 内向整流钾通道。最近，我们发现了这样一个 内向整流通道与支架蛋白 SAP97 之间的相互作用 在大脑中。该项目的目标是鉴定蛋白质复合物 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 渠道的活动。

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.