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 DmNaV (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 DmNaV 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 DmNaV variants generated sodium currents large enough for functional characterization. Among these variants, DmNaV5-1 and DmNaV7-1 channels activated at the most hyperpolarizing potentials, whereas DmNaV1-6 and DmNaV19 channels activated at the most depolarizing membrane potentials. We identified an A-to-I editing event in DmNaV5-1 that is responsible for its uniquely low-voltage-dependent activation. The wide range of voltage dependence of gating properties exhibited by DmNaV variants represents a rich resource for future studies to determine the role of DmNaV in regulating sodium channel gating, pharmacology, and neuronal excitability in insects.