MOLECULAR NEUROGENETICS OF DROSPHILA POTASSIUM CHANNELS

果蝇钾通道的分子神经遗传学

• 批准号: 3477962
• 负责人: Linda E Iverson
• 金额: $ 10.58万
• 依托单位: BECKMAN RES INST OF THE 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/3477962
• 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; 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+）通道是一个异常多样的离子通道 它们在选择K+而不是其他离子的能力上相似，但是 它们的动力学，电压依赖性，药理和单次 渠道行为。 由于其患病率和多样性，组织特异性 不同类别的K+通道的分布在 控制神经元活动。 不同类的K+频道已经 证明对几种生理功能有显着贡献 包括动作潜在的复极化，心脏起搏，神经元 破裂，学习和记忆。 该建议将检查分子 控制不同K+通道表达的机制 亚型及其在产生多种兴奋性中所扮演的作用 神经和肌肉的特性。 振荡器的分子分析（SH） 果蝇的基因座Melanogaster指示SH编码一个家庭 功能上不同的A型K+通道。 不同的SH基因产品是 以组织特异性表达，SH等位基因的表型表明 对特定组织中特定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 神经和肌肉将通过电生理分析研究 用异源表达的Sh cDNA转换的Sh突变档案 启动子（热休克蛋白70基因启动子）。 时间和空间 SH基因表达的模式和下层的分子机制 这些表达模式将通过组织化学染色来检查 用杂化基因转化的果蝇中的酶促活性在其中 酶报告基因的表达是由SH控制元件驱动的。 通过分析其他果蝇腿 - 被认为会影响SH编码的K+表达的摇动突变 频道。 SH的分析肯定会提供有关K+的新信息 可能在所有人的神经系统中起作用的通道调节机制 有机体。