PROPERTIES OF AXON TO GLIA GLUTAMATE SIGNALING

描述：(改编自申请者摘要)： 建议的研究是为了阐明保守的机制和功能 轴突神经胶质信号的意义。无脊椎动物的兴奋和 脊椎动物神经纤维激活突触和非突触释放 谷氨酸。在非突触部位，谷氨酸产生第二信使 被建议维持钾的变化和钙波 动态平衡对神经元兴奋性的保存及其影响 神经组织的新陈代谢、生长和分化。隐含的含义 这些研究表明，人们不能再认为发射机正在使用 只针对突触交流，但必须考虑到 潜在的向下传播轴突释放了一种递质代理， 调节其路径附近的所有或大多数细胞的反应。 这个概念的一个重要临床含义是病理性的 神经系统状况(例如中风、机械性头部 创伤、癫痫、缺血)谷氨酸钾积聚 细胞外间隙的异常可能会在突触上扰乱功能 和非突触，并导致细胞死亡。 这是第一次在完整的神经系统中进行系统的研究 谷氨酸释放的动力学、离子和动作电位依赖性 神经纤维，2)神经胶质和轴突谷氨酸运输的特性 谷氨酸从轴突释放的相关机制及3)贡献 神经胶质细胞对可释放谷氨酸代谢的影响。激励诱导释放 神经纤维中外源性和内源性谷氨酸的含量将通过 电泳法和层析法。离子替代，离子通道 阻滞剂和谷氨酸转运抑制剂将被用来描绘 发布过程的属性，并区分可能的

DESCRIPTION: (Adapted from Applicant's Abstract): The objective of the proposed study is to clarify the conserved mechanisms and functional significance of axon glial signaling. Excitation of invertebrate and vertebrate nerve fibers activates synaptic and non-synaptic release of glutamate. At non-synaptic sites, glutamate produces second messenger changes and calcium waves that are proposed to maintain potassium homeostasis for preservation of neuronal excitability, and to influence nerve tissue metabolism, growth, and differentiation. The implication of these studies is that one can no longer think of transmitters as being used for synaptic communication alone but one must consider that the action potential propagating down the axon releases a transmitter agent that modulates the responses of all or most cells in the proximity of its path. An important clinical implication of this concept is that pathological conditions of the nervous system (for example stroke, mechanical head trauma, epilepsy, ischemia) in which glutamate potassium accumulate abnormally in the extracelluar space may disrupt functions both synaptically and non-synaptically and lead to cellular death. This is the first systematic study in any intact nervous system of 1) the kinetics, ion, and action potential-dependence of the release glutamate from nerve fibers, 2) the properties of glial and axonal glutamate transport mechanism relevant to glutamate release from axons and 3) the contribution of glia to metabolism of releasable glutamate. Excitation-induced release of exogenous and endogenous glutamate from nerve fibers will be assessed by electrophoretic and chromatographic assays. Ion substitution, ion channel blocker, and glutamate transport inhibitors will be used to delineate the properties of the release process and to distinguish among the possible