Originally published as Genetics Published Articles Ahead of Print on February 1, 2006.

Genetics, Vol. 172, 2351-2358, April 2006, Copyright © 2006
doi:10.1534/genetics.105.048777

In Vivo Analysis of a Gain-of-Function Mutation in the Drosophila eag-Encoded K+ Channel

Robert J. G. Cardnell*,1, Damian E. Dalle Nogare*, Barry Ganetzky{dagger} and Michael Stern*

* Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77251-1892 and {dagger} Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706

1 Corresponding author: Department of Biochemistry and Cell Biology, MS-140, Rice University, P.O. Box 1892, Houston, TX 77251-1892.
E-mail: robertc{at}bioc.rice.edu

Neuronal Na+ and K+ channels elicit currents in opposing directions and thus have opposing effects on neuronal excitability. Mutations in genes encoding Na+ or K+ channels often interact genetically, leading to either phenotypic suppression or enhancement for genes with opposing or similar effects on excitability, respectively. For example, the effects of mutations in Shaker (Sh), which encodes a K+ channel subunit, are suppressed by loss-of-function mutations in the Na+ channel structural gene para, but enhanced by loss-of-function mutations in a second K+ channel encoded by eag. Here we identify two novel mutations that suppress the effects of a Sh mutation on behavior and neuronal excitability. We used recombination mapping to localize both mutations to the eag locus, and we used sequence analysis to determine that both mutations are caused by a single amino acid substitution (G297E) in the S2–S3 linker of Eag. Because these novel eag mutations confer opposite phenotypes to eag loss-of-function mutations, we suggest that eagG297E causes an eag gain-of-function phenotype. We hypothesize that the G297E substitution may cause premature, prolonged, or constitutive opening of the Eag channels by favoring the "unlocked" state of the channel.