Connexins in Neuronal and Glial Gap Junctions in CNS

描述(申请人提供)：缝隙连接是成对的薄膜 由密集的管状跨膜通道簇组成的专门化 (连接蛋白)连接细胞外间隙的头对头，形成 离子和细胞间的直接电耦合和交换途径 低分子代谢物。在哺乳动物中，缝隙连接非常丰富。 神经胶质细胞之间和最近被发现的“混合”(电气 加上化学物质)神经元之间的突触。缝隙连接由一个或 在两份人类草稿中发现的21种不同的连接蛋白中的更多 基因组序列。哺乳动物中枢神经系统至少表达13种连接蛋白。 目前，关于哪种连接蛋白存在相当大的争议 在神经元与神经胶质细胞之间，以及神经元是否通过连接与神经胶质细胞相连 缝隙连接。胶质细胞缝隙连接为维持离子连接提供了途径 中枢神经系统的动态平衡，而神经元的缝隙连接，特别是 那些处于混合突触的人可能是高频产生的基础 神经元的振荡是意识知觉和觉醒的底物 从睡眠中，它们可能参与了脑电的同步爆发活动 癫痫。因为几种连接蛋白的特定配对组合 在每个缝隙连接斑块中的表达提供代谢、电压和离子 调节间隙结电导和栅极特性，这是必不可少的 测定神经元和神经胶质细胞缝隙连接的连接蛋白组成 在正常的成年动物身上。此外，还必须确定，除了 连接神经元，缝隙连接将神经元连接到神经胶质细胞。因此，长期目标是 建议的研究是确定相对丰度，组织学 和超微结构分布、细胞偶联伙伴和连接蛋白 成年哺乳动物中枢神经系统神经元和神经胶质细胞缝隙连接的组成。

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.