This is a renewal application to continue studies on the molecular properties of potassium channels in Drosophila. By taking advantage of the relatively small genome size of the fruit fly, the investigator plans to define the entire complement of potassium channels in this organism, including voltage-dependent, calcium-dependent, and inward rectifier types. The guiding thesis in this proposal is that, in contrast to mammals, it seems that the fly has fewer members of each potassium channel subclass. One can therefore examine the specific contributions of each of the five known classes of potassium channels in the Drosophila system because there is no (known) complication due functional redundancy. In addition, the identification of a novel Drosophila potassium channel subclass may lead to the isolation of several novel mammalian homologues. The long-term plan is to obtain a 'blueprint' of the entire potassium channel system in the fly so that the contribution of any one channel subtype can eventually be related to its physiological and behavioral role in the adult organism. Novel potassium channel types that are first identified in flys will also be subsequently identified in mammals. Each of the cloned potassium channel subtypes will be functionally characterized in the Xenopus oocyte expression system and its cellular distribution within the fly will be determined by immunological methods. Finally, a reverse genetic approach using dominant-negative mutation strategy will be employed to identify roles of each channel subclass in fly development and behavior.
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