THE DROSOPHILA ERG K+ CHANNEL POLYPEPTIDE IS ENCODED BY THE SEIZURE LOCUS

The eag family of K+ channels contains three known subtypes: eag, elk, and erg. Genes representing the first two subtypes have been identifi ed in flies and mammals, whereas the third subtype has been defined on ly by the human HERG gene, which encodes an inwardly rectifying channe l that is mutated in some cardiac arrhythmias. To establish the predic ted existence of a Drosophila gene in the erg subfamily and to learn m ore about the structure and biological function of channels within thi s subfamily, we undertook a search for the Drosophila counterpart of H ERG. Here we report the isolation and characterization of the Drosophi la erg gene. We show that it corresponds with the previously identifie d seizure (sei) locus, mutations of which cause a temperature-sensitiv e paralytic phenotype associated with hyperactivity in the flight moto r pathway. These results yield new insights into the structure and evo lution of the eag family of channels, provide a molecular explanation for the sei mutant phenotype, and demonstrate the important physiologi cal roles of erg-type channels from invertebrates to mammals.