Connexins in Neuronal and Glial Gap Junctions in CNS

描述（由申请人提供）：间隙连接是成对的膜 由密集的管状跨膜通道簇组成的特化 （连接体）连接头到头穿过细胞外空间，形成 直接电耦合和细胞间离子交换的途径， 低分子量代谢物。在哺乳动物中， 神经胶质细胞之间，最近已经发现在“混合”（电 加上化学）神经元之间的突触。缝隙连接由一个或多个 在两份人类基因组草图中鉴定的21种不同的连接蛋白中， 基因组序列至少有13种连接蛋白在哺乳动物中枢神经系统中表达。 目前，存在相当大的争议， 在神经元与神经胶质中，以及神经元是否通过联合 缝隙连接胶质细胞间隙连接为维持离子通道 在整个中枢神经系统的稳态，而神经元间隙连接，特别是 那些在混合突触，可能是基础的生产高频率 神经元的振荡作为有意识感知和唤醒的基底 从睡眠中，他们可能参与同步爆发活动， 癫痫因为几种连接蛋白的特定配对组合 在每个间隙连接斑块中表达的蛋白质提供了代谢、电压和离子 调节间隙连接电导和门控特性， 以确定神经元和神经胶质细胞间隙连接的连接蛋白组成 在正常的成年动物中。此外，还必须确定， 连接神经元的缝隙连接将神经元与神经胶质连接起来。因此，长期目标 建议的研究是确定相对丰度，组织学 和超微结构分布，细胞偶联伴侣，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间隙连接的组成。

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.