FUNCTIONAL ANALYSIS OF DROSOPHILA ERG POTASSIUN CHANNELS

这个项目的目标是了解果蝇的作用 乙醚--GO-GO(Erg)钾通道在膜兴奋性中的作用。具体来说， 这种蛋白质的结构/功能关系，以及这种蛋白质是如何 参与膜兴奋性，及其功能后果 将通过生物物理来评估改变通道结构的可能性， 神经细胞和突变研究。因为人类形体(Herg) 这种K+通道与潜在的致命心律失常有关， 从这项研究中收集的信息应该与 人类的状况。 对异源表达的ERG K+通道的检查将确定 该通道的生物物理参数允许进行比较 与其他K+通道的关系，并为研究 这个频道在它更自然的蜂窝环境中。一次考试 在分离的神经元中这一通道的研究将提供关于 该通道在调节膜兴奋性方面起着重要作用 为该亚家族的神经功能提供新的信息 K+通道。对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和 展示改变这些领域的后果。总体而言，这 该提案将增加我们对K+通道生物学和 洞察细胞膜疾病的潜在原因 兴奋性。

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.