Molecular characterization and functional expression of the DSC1 channel

Abstract

Drosophila Sodium Channel 1 (DSC1) was predicted to encode a sodium channel based on a high sequence similarity with vertebrate and invertebrate sodium channel genes. However, BSC1, a DSC1 ortholog in Blattella germanica, was recently shown to encode a cation channel with ion selectivity toward Ca2+. In this study, we isolated a total of 20 full-length cDNA clones that cover the entire coding region of the DSC1 gene from adults of Drosophila melanogaster by reverse transcription-polymerase chain reaction. Sequence analysis of the 20 clones revealed nine optional exons, four of which contain in-frame stop codons; and 13 potential A-to-I RNA editing sites. The 20 clones can be grouped into eight splice types and represent 20 different transcripts because of unique RNA editing. Three variants generated DSC1 currents when expressed in Xenopus oocytes. Like the BSC1 channel, all three functional DSC1 channels are permeable to Ca2+ and Ba2+, and also to Na+ in the absence of external Ca2+. Furthermore, the DSC1 channel is insensitive to tetrodotoxin, a potent and specific sodium channel blocker. Our study shows that DSC1 encodes a voltage-gated cation channel similar to the BSC1 channel in B. germanica. Extensive alternative splicing and RNA editing of the DSC1 transcripts suggest the molecular and functional diversity of the DSC1 channel.