ION CHANNEL EXPRESSION IN PERIPHERAL NERVOUS SYSTEM

这项修订后的计划项目赠款的广泛目标是揭示 控制基因表达的分子机制 电压依赖性离子通道，并了解如何 表达和亚细胞靶向的不同成员， 基因家族有助于细胞特异性放电特性， 神经元该计划的主旨是解决这些问题， 周围神经系统（PNS）的问题，但比较 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寻求确定具体的 神经元中的钠通道结构。战略是 比较alpha和附件的功能“指纹” 钠通道亚基在非洲爪蟾卵母细胞中表达， PC12细胞差异表达的钠电流指纹图 细胞通过刺激不同的信号转导 途径。 目标2是比较控制钠的机制 PNS和CNS中的通道基因表达。DNA元素和 神经特异性表达所需的转录因子 一个钠通道基因只在PNS神经元中表达， 鉴定受体结构域与细胞质分子 参与钠通道上调的中间体 神经元生长因子基因将通过以下方法鉴定： 多种生物化学和遗传学方法。目标3：揭示 涉及靶向钠的分子机制， 钾通道到不同的亚细胞结构域。的针对 PC12和MDCK细胞系，以及神经元，将使用 遗传、生物化学和免疫化学方法。所有这些 目标利用该计划提供的独特试剂 investigators.核心设施将提供支持，设备， 分子生物学、组织工程学和生物技术领域的试剂和技术专长 文化和行政职能。这个项目有 可能导致新的治疗策略 感觉和交感神经的病理学。这些研究也代表了 这是理解离子如何 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.