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.
