A comparative study of voltage-gated sodium channels in the Insecta: implications for pyrethroid resistance in Anopheline and other Neopteran species.

We report the complete cDNA sequence of the Anopheles gambiae voltage-gated sodium channel (VGSC) alpha-subunit isolated from mature adult mosquitoes. The genomic DNA contains 35 deduced exons with a predicted translation of <or= 2139 amino acid cDNAs. The transcription of the gene is, however, complex, alternate splicing being evident for at least five optional exons (or exon segments) and two sets of mutually exclusive exons. Overall gene organization was also compared with that of other VGSCs within the Insecta. Several insecticides used in mosquito control (including DDT and synthetic pyrethroids) target the VGSC. Isolation of the sodium channel cDNA for An. gambiae: (1) allows prediction of likely single nucleotide polymorphisms that may arise at residue L1014 to cause resistance to insecticides; (2) defines An. gambiae exon usage in key areas of the VGSC protein that are known (from previous studies in a range of different pest species) to have roles in altering insecticide susceptibility and in generating resistance; and (3) is a critical first step towards development of refined malarial control strategies and of new diagnostics for resistance monitoring.