ION CHANNEL EXPRESSION IN PERIPHERAL NERVOUS SYSTEM

这项修订计划项目拨款的主要目标是揭示 编码基因表达调控的分子机制 电压依赖的离子通道，并了解 基因不同成员的表达和亚细胞靶向 基因家族在细胞特异性激发特性中起作用 神经元。该计划的主旨是解决这些问题 外周神经系统(PNS)的问题，但比较 建议在PNS和CNS中的通道之间 信息提供了对控制机制的具体见解。 目标L力求找出具体的职能对应者 神经元中的钠通道结构。战略将是 比较字母和附件的功能“指纹” 钠通道亚基在非洲爪哇卵母细胞中的表达 PC12细胞钠电流差异表达的指纹图谱 通过刺激不同的信号转导来刺激细胞 小路。目标2是比较钠的控制机制 通道基因在三叉神经节和中枢神经系统中的表达。DNA元素和 神经特异性表达所需的转录因子 一种仅在三叉神经节神经元中表达的钠通道基因将是 已确认身份。受体结构域与细胞质分子 参与钠通道上调的中间体 神经生长因子的基因将通过 多种生化和遗传方法。目标3是揭示 靶向钠离子和钠离子的分子机制 钾通道通向不同的亚细胞结构域。瞄准目标 PC12和MDCK细胞系，以及神经元中，将使用 遗传、生化和免疫化学方法。所有这些都是 Goals利用该计划提供的独特试剂 调查人员。核心设施将提供支持、设备、 试剂和分子生物学、组织方面的技术专长 文化和行政职能。该计划项目有 为治疗带来新策略的潜力 感官和交感的病理。这些研究还代表了 了解离子如何存在的重要的第一步 参与疼痛通路的通道在体内受到调节。

The broad goal of this revised program project grant is to reveal the molecular mechanisms controlling expression of genes encoding voltage-dependent ion channels, and to understand how the expression and subcellular targeting of different members of the gene family contribute to cell-specific firing properties in neurons. The thrust of the program is towards addressing these issues in the peripheral nervous system (PNS), but comparisons between channels in the PNS and CNS are proposed where this information provides specific insights into control mechanisms. Goal l seeks to identify the functional counterparts of specific sodium channel structures in neurons. The strategy will be to compare the functional "fingerprints" of alpha and accessory sodium channel subunits expressed in Xenopus oocytes with the fingerprints of sodium currents expressed differentially in PC12 cells through stimulation of distinct signal transduction pathways. Goal 2 is to compare the mechanisms controlling sodium channel gene expression in the PNS and CNS. The DNA elements and transcription factors required for neural-specific expression of a sodium channel gene expressed exclusively in PNS neurons will be identified. Receptor domains and cytoplasmic molecular intermediates involved in the up-regulation of sodium channel genes by neuronal growth factors will be identified through multiple biochemical and genetic approaches. Goal 3 is to reveal the molecular mechanisms involved in targeting of sodium and potassium channels to distinct subcellular domains. Targeting in PC12 and MDCK cell lines, and in neurons, will be studied using genetic, biochemical, and immunochemical approaches. All of these goals exploit unique reagents provided by the program investigators. Core facilities will provide support, equipment, reagents, and technical expertise for molecular biology, tissue culture, and administrative functions. This program project has the potential to lead to new strategies for therapeutic treatment of sensory and sympathetic pathologies. The studies also represent an important first step toward an understanding of how ion channels involved in pain pathways are modulated in vivo.