EFFECT OF PERMEANT IONS ON NMDA CHANNEL BLOCK BY MG2+.

MG2 对 NMDA 通道阻滞的永久离子的影响。

• 批准号: 6013289
• 负责人: ANQI QIAN
• 金额: $ 3.04万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-03 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6013289
• 关键词: NMDA receptors; brain cell; calcium channel; laboratory rat; magnesium ion; receptor binding; tissue /cell culture; voltage /patch clamp; voltage gated channel

DESCRIPTION: (Applicant's Description) The N-methyl-D-aspartate (NMDA) receptor is involved in many neuronal functions. The research outlined in this proposal is focused upon a powerful form of regulation of the NMDA receptor: the voltage-dependent channel block by external Mg2+. Using the approaches of electrophysiology, kinetic modeling, and molecular biology, the applicant wishes to expand our knowledge of: (1) the characteristics and mechanism of the effects of permeant ions on Mg2+ block of the NMDA receptor in cortical neurons; (2) the NMDA receptor subunit specificity of the permeant ion effects; and (3) the molecular elements that contribute to the permeant ion effects. Since the NMDA receptor is one of the most fundamentally important macromolecules, by virtue of its wide distribution and unique properties, information regarding its basic characteristics will give insight into all the normal and abnormal processes in which the NMDA receptor is involved. Specifically, this research addresses several issues of significance to the physiology and pathology of mental health: (1) This research may shed light on variation in receptor channel function during synaptic transmission, when transient but drastic change occurs in external Na+ concentration. (2) This research may reveal altered receptor function under ischemic conditions, when permeant ion concentrations change from their normal level. (3) This research contributes to the characterization of the ion binding sites of the NMDA receptor which will help us understand the detailed features of this receptor and how its structure results in its unique functional properties.

描述：（申请人的描述） N-甲基-D-天冬氨酸 (NMDA) 受体参与许多神经元 功能。本提案中概述的研究重点是一个强大的 NMDA 受体的调节形式：电压依赖性通道阻断 外部 Mg2+。使用电生理学、动力学建模和 分子生物学，申请人希望扩展我们的知识：（1） 渗透离子对Mg2+块体影响的特性及机理 皮质神经元中的 NMDA 受体； (2) NMDA受体亚基 渗透离子效应的特异性； (3) 分子元素 有助于渗透离子效应。 由于 NMDA 受体是最重要的受体之一 大分子凭借其广泛的分布和独特的性质， 有关其基本特征的信息将有助于深入了解所有 NMDA 受体参与的正常和异常过程。 具体来说，这项研究解决了对 心理健康的生理学和病理学：（1）这项研究可能揭示 突触传递过程中受体通道功能的变化，当 外部Na+浓度发生短暂但剧烈的变化。 (2) 这个 研究可能揭示缺血条件下受体功能的改变 渗透离子浓度从正常水平发生变化。 （三）本研究 有助于 NMDA 离子结合位点的表征 受体，这将帮助我们了解该受体的详细特征 以及它的结构如何产生其独特的功能特性。