Glutamate Gated Channels in Central & Peripheral Neurons

中环谷氨酸门控通道

• 批准号: 6623574
• 负责人: James E Huettner
• 金额: $ 28.76万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6623574
• 关键词: AMPA receptors; NMDA receptors; central nervous system; confocal scanning microscopy; gene targeting; genetically modified animals; glutamate receptor; glutamates; guanosinetriphosphatases; hippocampus; immunofluorescence technique; in situ hybridization; laboratory mouse; neural transmission; neurons; neuroregulation; neurotransmitter transport; northern blottings; peripheral nervous system; polymerase chain reaction; protein structure function; receptor expression; synapses; tissue /cell culture; voltage /patch clamp

DESCRIPTION (provided by applicant): The long-term objective of my work is to provide a better understanding of synaptic transmission by studying the operation of NMDA, AMPA, and kainate receptors, which form ion channels gated by the neurotransmitter glutamate. Another major goal is to uncover properties of these receptors that may allow for clinical intervention to prevent excitotoxic cell death or to provide analgesia. The experiments outlined in this application focus on the regulation of kainate receptor composition and on the regulation of AMPA receptor sub-cellular distribution. In a series of studies on the electrophysiology of kainate receptors in neurons from the hippocampus, spinal cord and dorsal root ganglia, we have shown that each of these cell populations express kainate receptors with distinct pharmacological properties. The experiments in Specific Aim 1 will use molecular biology, physiology and subunit deficient mice to investigate the structural basis for these differences. Specific Aim 2 is focused on the role of specific kainate receptor subunits in spinal synaptic transmission. We have recently demonstrated three different ways in which kainate receptors participate in synaptic transmission in the dorsal horn of the spinal cord. Experiments in this aim will seek to determine whether the G1uR5 or GIuR6 subunits are required for the postsynaptic kainate receptors that mediate a component of primary afferent transmission, or for the presynaptic kainate receptors that modulate transmitter release from primary afferents and from spinal interneurons. The third major Aim of this application is to investigate the control of glutamate receptor distribution on hippocampal neurons by the low molecular weight GTPase rab 5 and other components of the endocytic trafficking pathway.

描述（由申请人提供）：我工作的长期目标是 通过研究突触传递提供更好的理解 NMDA、AMPA 和红藻氨酸受体的运作，形成门控离子通道 由神经递质谷氨酸。另一个主要目标是发现属性 这些受体可能允许临床干预以预防 兴奋性毒性细胞死亡或提供镇痛作用。中概述的实验 本申请重点关注红藻氨酸受体组成的调节以及 AMPA 受体亚细胞分布的调节。在一系列的 神经元红藻氨酸受体电生理学研究 海马体、脊髓和背根神经节，我们已经证明，每一个 这些细胞群表达具有独特药理学作用的红藻氨酸受体 特性。具体目标 1 中的实验将使用分子生物学， 生理学和亚基缺陷小鼠研究结构基础 这些差异。具体目标 2 重点关注特定红藻氨酸的作用 脊髓突触传递中的受体亚单位。我们最近有 证明了红藻氨酸受体参与的三种不同方式 脊髓背角的突触传递。实验于 该目标将寻求确定 G1uR5 或 GIuR6 亚基是否是 突触后红藻氨酸受体介导的组成部分所需 初级传入传输，或突触前红藻氨酸受体 调节初级传入神经和脊髓的递质释放 中间神经元。该应用程序的第三个主要目标是调查 低谷氨酸受体对海马神经元分布的控制 分子量 GTPase rab 5 和内吞运输的其他成分 途径。