CHEMICAL & MOLECULAR PROPERTIES OF ION CHANNEL PROTEINS

化学

基本信息

批准号：
3395419
负责人：
TED B BEGENISICH
金额：
$ 19.45万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
1977
资助国家：
美国
起止时间：
1977-12-01 至 1994-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3395419
关键词：
Cephalopoda amino group cell membrane chemical structure function divalent cations drug design /synthesis /production electrophysiology membrane activity membrane channels molecular dynamics nervous system disorder chemotherapy neurons optical polarization potassium channel protein structure function sodium channel

项目摘要

This research represents an interdisciplinary approach designed to elucidat chemical and molecular details of the ion channel proteins in the surface membranes of neuronal cells. In order to reach these goals several types of electrophysiological measurements will be combined with biochemical and optical techniques. Two types of neuronal preparations will be used for different projects in order exploit the advantages of The squid giant axon is especially well-suited to measurements of fast electrical signals like ion channel gating currents and for examining various optical signals. The cill bodies ef this axon are useful in measuring single channel currents and, because the Na channels are absent for several days after cell dissociation, can be used for studying Na and K channel gating currents in isolation. Since, unlike the axon, these neurons are not enveloped by Schwann cells, ion channel currents can more accurately be measured. The specific aims include: (1) determining the functional importance of amino groups on the external surface of the K channel protein, (2) determining th role of divalent cations in conformational changes of K channel proteins, (3) identifying the chemical group(s) forming the internal and external divalent cation binding sites of K channels, and (4) using quantitative analysis of electrophysiological and optical data to identify some molecula details of the conformational change process of Na and K channels. The results of this research will improve our basic understanding of the structure-function relation of ion channel proteins in neuronal cells. Thes ion channels are the targets of a variety of pharmacological and therapeuti agents and are involved in many neurological diseases. Therefore, an improved understanding of these proteins will aid in the improvement of dru design and in the treatment of neurological dysfunction.

这项研究代表了一种跨学科方法，旨在阐明表面离子通道蛋白的化学和分子细节神经元细胞膜。为了实现这些目标，有几种类型电生理测量将与生化和光学技术。两种类型的神经元制剂将用于不同的项目以利用鱿鱼巨轴突的优势特别适合快速电信号的测量，例如离子通道门控电流并用于检查各种光信号。这细胞体 ef 该轴突可用于测量单通道电流并且，因为细胞后几天 Na 通道不存在解离，可用于研究 Na 和 K 通道门控电流隔离。因为与轴突不同，这些神经元没有被施万细胞，可以更准确地测量离子通道电流。这具体目标包括：（1）确定氨基的功能重要性 K 通道蛋白外表面的基团，(2) 确定二价阳离子在 K 通道蛋白构象变化中的作用， (3) 识别形成内部和外部的化学基团 K 通道的二价阳离子结合位点，以及 (4) 使用定量分析电生理学和光学数据以识别某些分子 Na和K通道构象变化过程的细节。这这项研究的结果将提高我们对神经元细胞中离子通道蛋白的结构与功能关系。论文离子通道是多种药理和治疗的靶点剂并涉及许多神经系统疾病。因此，一个加深对这些蛋白质的了解将有助于改善 dru 设计和治疗神经功能障碍。