Functional and pharmacological characterization of sixty-four para sodium channel variants from Drosophila melanogaster in Xenopus oocytes.

摘要

Extensive alternative splicing and RNA editing of para, the voltage-gated sodium channel of Drosophila melanogaster, has been documented. However, the functional consequences of these post-transcriptional modifications have not yet been investigated. In this study we report the isolation, expression, and functional characterization of sixty-four full-length para cDNA clones. The sixty-four clones were grouped into twenty-nine splice types based on alternative exon usage. Functional analysis of these variants revealed a broad spectrum of voltage-dependences of activation and to a lesser extent, voltage dependences of inactivation. Sequence comparison of three functionally distinct variants uncovered novel A to I editing sites. Furthermore, differential sensitivities to an alpha-scorpion toxin, LghalphaIT, were revealed. The observed functional and pharmacological diversity of para variants supports the notion that alternative splicing and RNA editing are the two major mechanisms for generating sodium channel diversity in insects.