Mechanisms of N-Methyl-D-Aspartate Receptor-Channel Function

N-甲基-D-天冬氨酸受体通道功能的机制

• 批准号: 9222323
• 负责人: Linda Nowak
• 金额: $ 20.45万
• 依托单位: Cornell Univ - State: AWDS MADE PRIOR MAY 2010
• 依托单位国家: 美国
• 项目类别: Continuing grant
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-04-15 至 1997-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9222323&HistoricalAwards=false
• 关键词: Mechanisms; Methyl; Aspartate; Receptor; Channel

Dr. Nowak's research is aimed at obtaining additional knowledge of the mechanisms underlying N-methyl-D-aspartate (NMDA) receptor-channel function in mammalian brain neurons. The NMDA subclass of glutamate receptors are coupled to nonselective cation channels permeable to Ca2+ and blocked by Mg2+ in a voltage-dependent way. It is Ca2+ entry through NMDA channels which is thought to serve as a trigger for some of the plastic changes observed during nervous system development and in learning. Thus, the overall goal of the research is to address the question, "how can the apparently high influx of Ca2+ through NMDA channels as demonstrated by dye measurements be reconciled with all of the factors which would tend to limit Ca2+ entry"? One possible explanation is that there is more diversity among NMDA receptor-channels than previously recognized with some putative forms of the channels being relatively insensitive to blockage by Mg2+. Dr. Nowak's first series of experiments will involve an examination of the similarities and differences in biophysical parameters between NMDA channels in cerebellar granule cells and cortical neurons where different forms of the channels are predicted to occur. She will then perform additional experiments designed to examine the potential sites of Ca2+ interaction with NMDA channels. All of the proposed experiments are designed to explore the fundamental role(s) played by two divalent cations found in physiological fluids, namely Ca2+ and Mg2+ ions, in regulating the functioning of a major class of neurotransmitter-activated receptor-channels in brain neurons.

诺瓦克博士的研究旨在获得更多关于 N-甲基-D-天冬氨酸（NMDA）的作用机制 哺乳动物脑神经元中的受体通道功能。 所述NMDA 谷氨酸受体亚类与非选择性阳离子偶联 通道可渗透Ca 2+和阻断Mg 2+在一个电压依赖性 路上了 据认为，通过NMDA通道的Ca 2+进入 作为一个触发器的一些塑料变化观察期间， 神经系统发育和学习。 因此，总体目标 研究的目的是解决这个问题，“显然， 如染料所示，Ca 2+通过NMDA通道大量内流 测量结果应与所有可能导致 限制钙离子进入” 一种可能的解释是， NMDA受体通道之间的多样性比以前更多 认识到一些假定形式的渠道， 对Mg 2+的阻断相对不敏感。 诺瓦克医生的第一次 一系列的实验将涉及检查 NMDA生物物理参数的异同 小脑颗粒细胞和皮层神经元中的通道， 预测会出现不同形式的信道。 她将 然后进行额外的实验， Ca 2+与NMDA通道相互作用的潜在位点。 所有 拟议的实验旨在探索基本的 生理学中发现的两种二价阳离子所起的作用 液体，即Ca 2+和Mg 2+离子，在调节功能， 一种主要的神经递质激活受体通道， 脑神经元