MOLECULAR NEUROGENETICS OF DROSPHILA POTASSIUM CHANNELS

果蝇钾通道的分子神经遗传学

• 批准号: 3477965
• 负责人: Linda E Iverson
• 金额: $ 10.91万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-01-01 至 1994-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3477965
• 关键词: Drosophilidae; RNA splicing; cell type; complementary DNA; developmental genetics; electrical potential; evoked potentials; gene expression; gene mutation; genetic promoter element; genetic transcription; in situ hybridization; membrane potentials; mutant; neurochemistry; neurons; neurophysiology; neurotransmitters; nucleic acid sequence; potassium channel; reporter genes; second messengers; stress proteins; transposon /insertion element

Potassium (K+) channels are an exceptionally diverse group of ion channels that are similar in their ability to select for K+ over other ions, but differ in their kinetic, voltage-dependent, pharmacological and single- channel behavior. Due to their prevalence and diversity, tissue-specific distribution of different classes of K+ channels plays a leading role in controlling neuronal activity. Different classes of K+ channels have been shown to contribute significantly to several physiological functions including action potential repolarization, cardiac pacemaking, neuron bursting and learning and memory. This proposal will examine the molecular mechanisms involved in controlling the expression of different K+ channel subtypes and the role these play in generating diverse excitability properties in nerve and muscle. Molecular analysis of the Shaker (Sh) locus of Drosophila melanogaster indicates the Sh encodes a family of functionally distinct A-type K+ channels. Different Sh gene products are expressed in a tissue-specific manner, and phenotypes of Sh alleles suggest a requirement for specific Sh gene products in particular tissues. The effects of indiscriminate Sh gene expression on excitability properties of nerve and muscle will be investigated by electrophysiological analysis of Sh mutant files transformed with Sh cDNAs expressed from a heterologous promoter (heat shock protein 70 gene promoter). Temporal and spatial patterns of Sh gene expression, and the molecular mechanisms underlying these expression patterns, will be examined by histochemical staining for enzymatic activity in flies transformed with hybrid genes in which expression of enzyme reported genes is driven by Sh control elements. Regulatory pathways will be dissected by analysis of other Drosophila leg- shaking mutations that are thought to affect expression of Sh encoded K+ channels. Analysis of Sh is certain to provide novel information about K+ channel regulatory mechanisms that may operate in the nervous system of all organisms.

钾 (K+) 通道是一组极其多样化的离子通道 与其他离子相比，它们选择 K+ 的能力相似，但是 它们的动力学、电压依赖性、药理学和单一性方面有所不同 渠道行为。 由于其普遍性和多样性，组织特异性 不同类别的 K+ 频道的分布起着主导作用 控制神经元活动。 不同类别的 K+ 频道已 显示对多种生理功能有显着贡献 包括动作电位复极、心脏起搏、神经元 爆发和学习和记忆。 该提案将检查分子 控制不同 K+ 通道表达的机制 亚型以及它们在产生不同兴奋性中所发挥的作用 神经和肌肉的特性。 摇床 (Sh) 的分子分析 果蝇基因座表明 Sh 编码一个家族 功能不同的 A 型 K+ 通道。 不同的Sh基因产物是 以组织特异性方式表达，Sh 等位基因的表型表明 特定组织中对特定 Sh 基因产物的需求。 这 不加选择的 Sh 基因表达对兴奋性特性的影响 将通过电生理分析来研究神经和肌肉 用异源表达的 Sh cDNA 转化的 Sh 突变体文件 启动子（热休克蛋白70基因启动子）。 时间和空间 Sh 基因表达模式及其分子机制 这些表达模式将通过组织化学染色进行检查 用杂种基因转化的果蝇的酶活性，其中 酶报告基因的表达由Sh控制元件驱动。 将通过分析其他果蝇腿来剖析监管途径 震动突变被认为影响 Sh 编码的 K+ 的表达 渠道。 对 Sh 的分析肯定会提供有关 K+ 的新信息 可能在所有神经系统中运作的通道调节机制 有机体。