MODULATION AND CHARACTERIZATION OF GLUTAMATE (AMPA) RECEPTORS

谷氨酸 (AMPA) 受体的调节和表征

• 批准号: 6301670
• 负责人: VISHNU D SUPPIRAMANIAM
• 金额: $ 3.04万
• 依托单位: TUSKEGEE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至 2000-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6301670
• 关键词: AMPA receptors; SDS polyacrylamide gel electrophoresis; electrochemistry; electrodes; electrophysiology; gap junctions; heparin; immunoprecipitation; laboratory rat; long term potentiation; membrane channels; mucopolysaccharides; neural plasticity; pharmacokinetics; protein reconstitution; psychotropic drugs; pyridine; receptor binding; receptor expression; synapses; voltage /patch clamp

Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) subtype of glutamate receptor is believed to be central to synaptic plasticity in the mammalian brain. It is implicated in epilepsy and excitoxicity. Thus the mechanisms and factors which modulate AMPA receptor activity are of considerable interest. The focus of this project is to determine the functional properties of AMPA receptors and associated ion channels by the use of compounds which modulate receptor function. The long-term objective is to uncover the role of AMPA receptors in synaptic plasticity and long term potentiation (LTP). LTP is a form of synaptic plasticity thought to underlie learning and memory. It is noted that during the purification process heparin bound with high affinity to solubilized AMPA receptors and altered their channel kinetics. The effects of heparin and other glycosaminoglycans (GAGs) on single channel kinetics of purified and reconstituted AMPA receptors will be determined. Biochemical studies indicated that heparin has little effect on membrane associated AMPA receptors. During reconstruction experiments heparin and dextran sulfate induced AMPA channels of very high conductivity. Thus this project will define the mechanism responsible for the differences in responses of membrane associated and solubilized receptors to glycosaminoglycans. This will be achieved by electrophysiological analysis of reconstituted. This will be achieved by electrophysiological analysis of reconstituted crude synaptic preparations that have been treated with specific enzymes to remove glycosaminoglycans. This project will also investigate the role of glycosaminoglycans on the increase cooperativity among AMPA receptor channels and the effects of centrally active drugs (benzoyl pyridine derivatives) on AMPA receptors and associated channels. These drugs have been shown to result in substantial improvement in retention scores of rats and human subjects tested on various memory tasks, possibly due to modulation of AMP receptors and associated ion channels.

Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic酸(AMPA)亚型 谷氨酸受体被认为是突触可塑性的中心。 哺乳动物的大脑。它与癫痫和兴奋性中毒有关。因此， 调节AMPA受体活性的机制和因素有 相当感兴趣。本项目的重点是确定 AMPA受体及其相关离子通道的功能特性 使用调节受体功能的化合物。长期目标 揭示AMPA受体在突触可塑性和长时程中的作用 术语增强(LTP)。LTP是突触可塑性的一种形式，被认为 学习和记忆是基础。请注意，在提纯过程中 与可溶性AMPA受体高亲和力结合的肝素和 改变了他们的通道动力学。肝素和其他药物的作用 糖胺多聚糖(GAG)对纯化和纯化的单通道动力学的影响 重组的AMPA受体将被确定。生化研究 提示肝素对膜相关AMPA影响不大。 感受器。在重建实验中，肝素和硫酸葡聚糖 诱导了非常高电导率的AMPA通道。因此，这个项目将 定义造成以下方面反应差异的机制 糖胺聚糖的膜结合和增溶受体。这 将通过电生理分析实现的重组。这 将通过对重组原油进行电生理分析来实现 已经用特定酶处理过的突触准备 去掉糖胺多糖。该项目还将调查 糖胺多糖对AMPA受体协同作用的影响 通道和中枢活性药物(苯甲酰吡啶)的作用 衍生物)在AMPA受体和相关通道上。这些药有 已被证明显著提高了对 大鼠和人类受试者在各种记忆任务上进行测试，可能是由于 AMP受体和相关离子通道的调节。