PROPERTIES OF AXON TO GLIA GLUTAMATE SIGNALING

描述：（改编自申请人的摘要）： 拟开展的研究旨在阐明其保守机制和功能 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 谷氨酸盐。 在非突触部位，谷氨酸产生第二信使 变化和钙波，建议保持钾 保持神经元兴奋性的稳态，并影响 神经组织代谢、生长和分化。 的含义 这些研究表明，人们不能再认为发射机被用于 但我们必须考虑到 电位沿轴突向下传播释放出一种递质， 调节其路径附近的所有或大多数细胞的反应。 这一概念的一个重要临床含义是， 神经系统的状况（例如中风、机械头 创伤、癫痫、局部缺血），其中谷氨酸钾积累 在细胞外空间的异常可能会破坏功能， 并且是非突触性的并导致细胞死亡。 这是第一次对任何完整的神经系统进行系统研究， 谷氨酸释放的动力学、离子和动作电位依赖性 神经纤维，2）胶质细胞和轴突谷氨酸转运的性质 与轴突释放谷氨酸有关的机制和3）贡献 对可释放谷氨酸代谢的影响。 兴奋诱发释放 将通过以下方法评估来自神经纤维的外源性和内源性谷氨酸盐 电泳和色谱分析。 离子替代，离子通道 阻断剂和谷氨酸转运抑制剂将用于描绘 释放过程的性质，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