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

诺瓦克博士的研究旨在获得哺乳动物脑神经元中n -甲基- d -天冬氨酸（NMDA）受体通道功能的机制的额外知识。谷氨酸受体的NMDA亚类以电压依赖的方式偶联于可渗透于Ca2+并被Mg2+阻断的非选择性阳离子通道。Ca2+通过NMDA通道进入被认为是神经系统发育和学习过程中观察到的一些可塑性变化的触发因素。因此，研究的总体目标是解决这个问题，“如何能通过NMDA通道明显高钙流入的染料测量证明与所有的因素，可能会限制Ca2+进入调和”？一种可能的解释是，NMDA受体通道的多样性比以前认识到的要多，一些假定的通道形式对Mg2+的阻断相对不敏感。诺瓦克博士的第一个系列实验将包括检查小脑颗粒细胞和皮质神经元中NMDA通道在生物物理参数上的异同，在皮质神经元中会出现不同形式的通道。然后，她将进行额外的实验，旨在检查Ca2+与NMDA通道相互作用的潜在位点。所有提出的实验都旨在探索生理液体中发现的两种二价阳离子（即Ca2+和Mg2+离子）在调节脑神经元中一类主要神经递质激活受体通道的功能方面所起的基本作用。

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.