MOLECULAR NEUROGENETICS OF DROSPHILA POTASSIUM CHANNELS

钾离子通道是一组非常多样化的离子通道 它们选择K+离子的能力与其他离子相似，但 不同的动力学，电压依赖性，药理学和单一的， 渠道行为 由于其普遍性和多样性，组织特异性 不同类型的K+通道的分布起着主导作用， 控制神经元活动 不同类型的K+通道已被 显示出对几种生理功能有显著贡献 包括动作电位复极、心脏起搏、神经元 爆发，学习和记忆。 这项提案将审查分子 参与控制不同K+通道表达的机制 亚型以及它们在产生不同兴奋性中的作用 神经和肌肉的特性。 振荡器（Sh）的分子分析 黑腹果蝇的基因座表明，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 在特定组织中需要特定的Sh基因产物。 的 不加选择的Sh基因表达对神经元兴奋性的影响 神经和肌肉将通过电生理分析进行研究， 用从异源表达的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）。 时空 Sh基因表达的模式，以及潜在的分子机制 将通过组织化学染色检测这些表达模式， 用杂交基因转化的果蝇中的酶活性，其中 酶报告基因的表达由Sh控制元件驱动。 调节途径将通过分析其他果蝇的腿- 被认为影响Sh编码的K+表达的震动突变 渠道 对Sh的分析肯定会提供有关K+的新信息 通道调节机制，可能在所有的神经系统运作， 有机体

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.