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The Journal of Neuroscience, October 15, 2000, 20(20):7517-7524

Mutants of a Temperature-Sensitive Two-P Domain Potassium Channel

Maya T. Kunkel¹, Duncan B. Johnstone³, James H. Thomas³, and Lawrence Salkoff^{1, 2}

Departments of ¹ Anatomy and Neurobiology and ² Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, and ³ Department of Genetics, University of Washington, Seattle, Washington 98195

Within the Caenorhabditis elegans genome there exist at least 42 genes encoding TWK (two-P domain K⁺) channels, potassium channel subunits that contain two pore regions and four transmembrane domains. We now report the first functional characterization of a TWK channel from C. elegans. Although potassium channels have been reported to be activated by a variety of factors, TWK-18 currents increase dramatically with increases in temperature. Two mutant alleles of the twk-18 gene confer uncoordinated movement and paralysis in C. elegans. Expression of wild-type and mutant TWK-18 channels in Xenopus oocytes showed that mutant channels express much larger potassium currents than wild-type channels. Promoter-green fluorescent protein fusion experiments indicate that TWK-18 is expressed in body wall muscle. Our genetic and physiological data suggest that the movement defects observed in mutant twk-18 animals may be explained by an increased activity of the mutant TWK-18 channels.

Key words: potassium channel; temperature; C. elegans; uncoordinated; mutant; TWIK; TASK; TREK; TRAAK; KCNK; unc-110; mah-2

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20207517-08$05.00/0

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