FUNCTIONAL ANALYSIS OF DROSOPHILA ERG POTASSIUN CHANNELS

果蝇 ERG 钾通道的功能分析

• 批准号: 2710088
• 负责人: BLAKE D ANSON
• 金额: $ 2.62万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-21 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2710088
• 关键词: Drosophilidae; Xenopus oocyte; animal genetic material tag; developmental neurobiology; gene induction /repression; gene mutation; invertebrate embryology; larva; molecular cloning; neurogenetics; neurons; potassium channel; protein structure function

The goal of this project is to understand the role of the Drosophila ether- -go-go (erg) K+ channel in membrane excitability. Specifically, the structure/function relationships of this protein, how this protein participates in membrane excitability, and the functional consequences of altering channel structure will be assessed through biophysical, neuronal, and mutational investigations. Since the human form (HERG) of this K+ channel is involved in potentially fatal cardiac arrhythmias, information gathered from this study should be directly relevant to the human condition. An examination of heterologously expressed erg K+ channels will define the biophysical parameters of this channel, allow comparisons to be made with other K+ channels, and provide information essential for study of this channel in its more native cellular environment. An examination of this channel in dissociated neurons will provide insight as to the role this channel plays in regulating membrane excitability as well as providing novel information on the neuronal function of this subfamily of K+ channels. A mutational analysis of erg K+ channels will allow elucidation of protein domains essential for channel function and demonstrate the consequences of altering such domains. Overall, this proposal will increase our understanding of K+ channel biology and provide insight as to the causes underlying disorders of membrane excitability.

这个项目的目标是了解果蝇的作用 乙醚-go-go（erg）钾离子通道的膜兴奋性。 具体而言， 这种蛋白质的结构和功能关系， 参与细胞膜的兴奋性， 将通过生物物理学， 神经元和突变研究。 人类形态（HERG） 与潜在的致命性心律失常有关， 从这项研究中收集的信息应直接与 人类的状况 检查异源表达的erg K+通道将定义 该通道的生物物理参数允许进行比较 与其他K+通道，并提供必要的信息，为研究 这个通道在其更原生的细胞环境中。 检查 这一通道在解离神经元将提供洞察力， 该通道在调节膜兴奋性以及 为该亚家族的神经元功能提供了新的信息 K+通道 erg K+通道的突变分析将允许 阐明通道功能所必需的蛋白质结构域， 展示了改变这些结构域的后果。 总体而言，这 该提案将增加我们对K+通道生物学的理解， 提供关于膜疾病的潜在原因的见解， 兴奋性