Connexins in Neuronal and Glial Gap Junctions in CNS

中枢神经系统神经元和胶质间隙连接中的连接蛋白

• 批准号: 6899799
• 负责人: JOHN E RASH
• 金额: $ 32.68万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6899799
• 关键词: animal tissue; central nervous system; confocal scanning microscopy; freeze etching; gap junctions; glia; immunocytochemistry; membrane channels; neuroanatomy; neurons; protein localization; protein structure function; synapses; transmission electron microscopy

DESCRIPTION (provided by applicant): Gap junctions are paired membrane specializations composed of dense clusters of tubular transmembrane channels (connexons) that link head to head across the extracellular space, forming pathways for direct electrical coupling and intercellular exchange of ions and low molecular weight metabolites. In mammals, gap junctions are abundant between glial cells and recently have been discovered at "mixed" (electrical plus chemical) synapses between neurons. Gap junctions are composed of one or more of the 21 different connexin proteins identified in the two draft human genome sequences. At least 13 connexin proteins are expressed in mammalian CNS. Currently, there is considerable controversy as to which connexins are present in neurons vs. glia, and whether neurons are coupled to glia through conjoint gap junctions. Glial gap junctions provide pathways for maintaining ionic homeostasis throughout the CNS, whereas neuronal gap junctions, particularly those at mixed synapses, may underlie the production of high-frequency oscillations in neurons as the substrate for conscious perception and arousal from sleep, and they may be involved in the synchronous bursting activity of epilepsy. Because the specific pairing combinations of the several connexins expressed in each gap junction plaque provide for metabolic, voltage, and ionic regulation of gap junction conductance and gating properties, it is essential to determine the connexin composition of both neuronal and glial gap junctions in normal adult animals. It also is essential to determine if, in addition to linking neurons, gap junctions link neurons to glia. Thus, the long-term goals of the proposed research are to determine the relative abundance, histological and ultrastructural distribution, cellular coupling partners, and connexin compositions of gap junctions in neurons and glia in adult mammalian CNS.

描述（申请人提供）：间隙连接是配对的膜 由管状跨膜通道的密集簇组成的专业 （连接）将头链接到细胞外空间，形成 直接电气耦合和离子间交换的途径和 低分子量代谢产物。在哺乳动物中，间隙连接丰富 在神经胶质细胞之间和最近在“混合”中发现了（电气 加上化学）神经元之间的突触。差距连接由一个或 在两个人草案中鉴定的21种不同连接蛋白中的更多 基因组序列。至少13个连接蛋白在哺乳动物中枢神经系统中表达。 目前，关于存在哪些连接素存在很大的争议 在神经元与神经胶质中，以及神经元是否通过联合耦合到神经胶质 间隙连接。神经胶质间隙连接提供了维持离子的途径 整个中枢神经系统中的稳态，而神经元间交界处，尤其是 混合突触的人可能是高频产量的基础 神经元的振荡作为有意识和唤醒的底物 从睡眠中，它们可能参与 癫痫。因为几种连接素的特定配对组合 在每个间隙连接斑块中表示代谢，电压和离子 间隙连接电导和门控性能的调节，这是必不可少的 确定神经元和神经胶质间隙连接的连接蛋白组成 在正常的成年动物中。除了 连接神经元，间隙连接将神经元与神经胶质联系起来。因此，长期目标 拟议的研究是确定相对丰度，组织学 以及超微结构分布，蜂窝耦合伙伴和连接蛋白 成年哺乳动物CNS中神经元和神经胶质间隙连接的组成。