Complementation of physiological and behavioral defects by a slowpoke Ca2+-activated K+ channel transgene

The Drosophila slowpoke gene encodes a large conductance calcium-activated potassium channel used in neurons, muscle, and some epithelial cells. Tissu e-specific transcriptional promoters and alternative mRNA splicing generate a large array of transcripts, These distinct transcripts are thought to ta ilor the properties of the channel to the requirements of the cell. Presuma bly, a single splice variant cannot satisfy the specific needs of all cell types. To test this, we examined whether a single slowpoke splice variant w as capable of complementing all slowpoke behavioral phenotypes, Null mutati ons in slowpoke cause animals to be semiflightless and to manifest an induc ible "sticky-feet" phenotype. The well-characterized slowpoke transcription al control region was used to direct the expression of a single slowpoke sp lice variant (cDNA H13) in transgenic flies. The endogenous gene in these f lies had been inactivated by the slo(4) mutation. Action-potential recordin gs and voltage-clamp recordings demonstrated the production of functional c hannels from the transgene, The transgene completely complemented the fligh t defect, but not the sticky-feet phenotype, We conclude that distinct slow poke channel isoforms, produced by alternative splicing, are not interchang eable and are required for proper function of different cell types.