TISSUE-SPECIFIC ALTERNATIVE SPLICING OF HYBRID SHAKER LACZ GENES CORRELATES WITH KINETIC DIFFERENCES IN SHAKER K+ CURRENTS IN-VIVO/

Alternative splicing of the Shaker (Sh) locus of Drosophila generates several transcripts with divergent 5' and 3' domains that produce kine tically distinct K+ currents in Xenopus oocytes. Although suggestive t hat alternative splicing may be involved in generating K+ channel dive rsity, clear tissue-specific differences in the distribution of partic ular Sh gene products have not been demonstrated. Using lacZ as a repo rter gene for accurate splicing of variable Sh 3' domains, we observe differences in beta-galactosidase expression patterns in transgenic an imals that indicate both temporal and spatial regulation of 3' splice choice. The differences in 3' splice choice can account for variation in recovery kinetics of Sh-encoded K+ currents recorded in adult flies . The results indicate that tissue-specific expression of functionally distinct Sh K+ channels is regulated, in part, at the level of pre-mR NA splicing and implicate sequences in or around the 3' splice site's in regulating the choice of 3' domain.