K+ channel complexes: assembly, trafficking and function

K 通道复合物：组装、运输和功能

基本信息

批准号：
10386964
负责人：
WILLIAM R KOBERTZ
金额：
$ 4.52万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-01 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10386964
关键词：
Actins Action Potentials Address Animal Disease Models Animal Model Arrhythmia Buffers Caliber Cardiac Cardiac Myocytes Cardiomyopathies Cavia Cell surface Cells Complex Data Detection Diffusion Dilated Cardiomyopathy Ensure Equilibrium Extracellular Domain Frequencies Funding Glycocalyx Goals Grant Heart Heart Contractilities Heart Diseases Heart failure Human Hypertrophic Cardiomyopathy Image Ion Channel Ion-Selective Electrodes Ions Kinetics Label Labyrinth Lighting Link Measures Membrane Methodology Molecular Mus Muscle Cells Myocardial Ischemia Myocardium Nerve Neurons Patients Periodicity Pharmacology Physical activity Physiological Potassium Potassium Channel Predisposition Proteins Protons Reagent Research Rodent Role Sampling Sarcolemma Shapes Signal Transduction Speed Structure Surface Technology Testing Training Tubular formation Uncertainty Ventricular Ventricular Arrhythmia Vestibule Visualization Wheat Germ Agglutinins base driving force effective therapy extracellular fluorophore heart cell heart function innovation mathematical model nanometer nanoscale polyhistidine sensor small molecule spatiotemporal stem trafficking

项目摘要

The long-term goal of this research is to elucidate the molecular and cellular mechanisms that ensure potassium (K+) channels assemble with the appropriate membrane-embedded regulatory subunits for proper physiological function in the heart, muscle, and nerve. In the previous funding period, we developed an innovative approach to label the t-tubules and sarcolemma of cardiomyocytes with either small molecule or protein-based K+-sensitive fluorophores. For this proposal, we will use our fluorescent bioconjugates to test the long standing hypothesis that K+ accumulates faster in the t-tubules to protect the heart during physical activity (Aim 1); to fluorescently visualize specific ion channel activity in order to identify the K+ channel/KCNE complexes responsible for maintaining cardiac rhythmicity (Aim 2). The completion of these aims will yield a transformative set of methodologies to directly investigate extracellular K+ accumulation from heart, muscle, and nerve cells isolated from healthy and disease animal models.

这项研究的长期目标是阐明分子和细胞机制确保钾（K+）通道与适当的膜装满的调节组装亚基在心脏，肌肉和神经中适当的生理功能。在上一个资助期，我们开发了一种创新的方法来标记T型管和肌膜具有小分子或基于蛋白质的K+敏感荧光团的心肌细胞。为了这提案，我们将使用我们的荧光生物缀合物来测试长期存在的假设K+ 在体育锻炼期间，在T管中积累更快的速度以保护心脏（AIM 1）；到荧光可视化特定的离子通道活动，以识别K+通道/KCNE 负责维持心脏节奏的复合物（AIM 2）。这些完成目的将产生一组变革性的方法，以直接研究细胞外K+ 从健康和疾病动物中分离出的心脏，肌肉和神经细胞积累型号。