Molecular and functional characterization of voltage-gated sodium channel variants from Drosophila melanogaster

Extensive alternative splicing and RNA editing have been documented for the transcript of DmNa(V) (formerly para), the sole sodium channel gene in Drosophila melanogaster. However, the functional consequences of these post-transcriptional modifications are not well understood. In this study we isolated 64 full-length DmNa(V) cDNA clones from D. melanogaster adults. Based on the usage of 11 alternative exons, 64 clones could be grouped into 29 splice types. When expressed in Xenopus oocytes, 33 DmNa(V) variants generated sodium currents large enough for functional characterization. Among these variants, DmNa(V)5-1 and DmNa(V)7-1 channels activated at the most hyperpolarizing potentials, whereas DmNa(V)1-6 and DmNa(V)19 channels activated at the most depolarizing membrane potentials. We identified an A-to-I editing event in DmNa(V)5-1 that is responsible for its uniquely low-voltage-dependent activation. The wide range of voltage dependence of gating properties exhibited by DmNa(V) variants represents a rich resource for future studies to determine the role of DmNa(V) in regulating sodium channel gating, pharmacology, and neuronal excitability in insects.