In the past two years a new family of potassium (K+) channels has been identified in mammals, C. elegans, Drosophila and plants. Members of this novel family possess two-pore regions and four transmembrane domains and are predicted to function as leak channels within each cell. By contributing to the K+ leak conductance, these K+ channels control the resting potential of the cell and can dramatically influence cell excitability. Accordingly, allelic variations of the genes encoding these channels conceivably could confer a genetic predisposition to seizure disorders. Analysis of over 90% of the C. elegans genome has indicated that there are many distinct members within this family. Preliminary results in C. elegans indicate that two-pore channels are expressed in small subset of cells within specific cell types. Given a similarly restrictive expression pattern in humans, two-pore K+ channels may serve as pharmacological targets in order to regulate the excitability of very specific cell types without many adverse side effects. Electrophysiological recordings of currents elicited by two- pore K+ channels analyzed by expression in Xenopus oocytes and the cell specific expression patterns of these channels will be examined in live C. elegans. Furthermore, genetic techniques will be employed using a C. elegans two-pore K+ channel mutant in order to determine the regulation of currents through these channels. Combined, these studies will contribute to our understanding of the physiological role of these channels in vivo.
