CHEMICAL & MOLECULAR PROPERTIES OF ION CHANNEL PROTEINS

化学

基本信息

批准号：
2262590
负责人：
TED B BEGENISICH
金额：
$ 20.23万
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 1995-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2262590
关键词：
alternatives to animals in research 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 squid

项目摘要

This research represents an interdisciplinary approach designed to elucidate 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. 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 of 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 the 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 molecular 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. These ion channels are the targets of a variety of pharmacological and therapeutic agents and are involved in many neurological diseases. Therefore, an improved understanding of these proteins will aid in the improvement of drug design and in the treatment of neurological dysfunction.

这项研究代表了一种跨学科方法，旨在阐明离子通道蛋白的化学和分子细节神经元细胞的表面膜。为了实现这些目标几个电生理测量的类型将与生物化学和光学技术。两种类型的神经元制剂将用于不同的项目。鱿鱼的巨轴突尤其如此非常适合离子通道等快速电信号的测量选通电流并用于检查各种光信号。细胞体该轴突的测量可用于测量单通道电流，并且，因为 Na 通道在细胞解离后几天不存在，可以用于研究隔离的 Na 和 K 通道门控电流。自从，与轴突不同，这些神经元不被施万细胞包裹，离子可以更准确地测量通道电流。具体目标包括：（1）确定氨基对 K 通道蛋白的外表面，(2) 确定的作用 K 通道蛋白构象变化中的二价阳离子，(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确定一些 Na和K构象变化过程的分子细节渠道。这项研究的成果将提高我们的基础了解离子通道蛋白的结构与功能关系神经元细胞。这些离子通道是多种细胞的靶标药理学和治疗剂，并涉及许多神经系统疾病。因此，加深对这些蛋白质将有助于改进药物设计和治疗神经功能障碍。