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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+）通道与适当的膜包埋调节心脏、肌肉和神经中正常生理功能的亚基。上一在资助期间，我们开发了一种创新的方法来标记T-小管和肌膜，心肌细胞与小分子或蛋白质为基础的K+敏感的荧光团。为此建议，我们将使用我们的荧光生物共轭物来测试长期存在的假设，K+ 在t-小管中积累更快，以在体力活动期间保护心脏（目的1）; 荧光显示特定离子通道活性，以鉴定K+通道/KCNE 负责维持心脏节律的复合物（目的2）。完成这些目标将产生一套变革性的方法，直接研究细胞外K+ 从健康和患病动物分离心脏、肌肉和神经细胞中积累模型