CHEMICAL SYNAPSES-BIOPHYSICAL STUDIES

化学突触-生物物理学研究

• 批准号: 6457322
• 负责人: Henry A. Lester
• 金额: $ 5万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-12-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6457322
• 关键词: GABA receptor; biophysics; conformation; electrophysiology; fluorescent dye /probe; laboratory mouse; membrane transport proteins; neurotransmitter transport; nicotinic receptors; protein structure function; purinergic receptor; site directed mutagenesis; synapses

This project focuses on the functional characteristics of molecules that render "fast" synapses, exquisite electrochemical machines, specialized to function on a time scale of milliseconds and a distance scale of micrometers. 1. Functional studies will continue on the nicotinic receptor superfamily. Tethered agonists and cation-it interactions will be studied. Fluorescent probes of receptor conformation will be developed and studied. 2. Structure/function relations will be studied in the P2X receptor superfamily. The mechanism for the large pore that appears after sustained exposure to ATP will be explored. The disulfide topology of the extracellular region will be explored. Mechanisms will be studied for the functional interaction between P2X and nicotinic receptors. 3. The experiments will develop ways to count local densities Of synaptic proteins: transporters, starting with the mouse GABA transporter mGAT1; and receptors, starting with the nAChR alpha4 subunit and P2X2 subunit Ion channels and transporters, including but not limited to those involved in synaptic transmission, are important in many aspects of pathophysiology and therapeutics.

这个项目的重点是分子的功能特征，这些分子可以产生“快速”突触，精致的电化学机器，专门在毫秒级的时间尺度和微米级的距离尺度上工作。1. 对烟碱受体超家族的功能研究将继续进行。栓系激动剂和阳离子相互作用将被研究。受体构象的荧光探针将被开发和研究。2. 我们将研究P2X受体超家族的结构/功能关系。将探讨持续暴露于ATP后出现的大孔的机制。将探讨细胞外区域的二硫拓扑结构。我们将进一步研究P2X与烟碱受体之间的功能相互作用机制。3. 该实验将开发计算突触蛋白转运体局部密度的方法，从小鼠GABA转运体mGAT1开始；离子通道和转运体，包括但不限于参与突触传递的离子通道和转运体，在病理生理学和治疗学的许多方面都很重要。