K+ currents play a major role in membrane excitability. Repolarizing outward currents are carried almost exclusively by K+. K+ channel conductances and/or distributions of K+ channels may be modulated in order to generate excitable membrane diversity. Although much is known about K+ channel physiology and pharmacology, relatively little is known about its molecular basis. The present research uses electrophysiological and molecular genetic methods to examine K+ channels. The goal is to provide a molecular understanding of K+ channel structure and function. Experiments focus on the Shaker (Sh) gene complex in Drosophila that encodes K+ channels. Functional features of K+ channel molecules altered by mutations will be deduced from single ion channel voltage clamp (patch clamp) experiments on Sh mutants. Molecular cloning experiments will provide a physical description of Sh genes at the molecular level, localize DNA sequences altered by Sh mutations, and provide the basis for subsequent biochemical isolation and characterization of K+ channel molecules. Structure-function relationships will be determined from comparisons of molecular genetic mapping and electrophysiology experiments on Sh mutants. Thus, the different molecular domains responsible for different channel functions may be determined. Sh is one of the best-studied sets of nervous system genes. Physiological, genetic, and molecular genetic analyses of Sh provide basic research with important implications for any nervous system disease with a heritable component.

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National Institute of Neurological Disorders and Stroke (NINDS)
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Genetics Study Section (GEN)
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California Institute of Technology
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