Conservation of the voltage-sensitive sodium channel protein within the Insecta

Abstract

The voltage-sensitive sodium channel (VSSC) is essential for the generation and propagation of action potentials. VSSC kinetics can be modified by producing different splice variants. The functionality of VSSC depends on features such as the voltage sensors, the selectivity filter and the inactivation loop. Mutations in Vssc conferring resistance to pyrethroid insecticides are known as knockdown resistance (kdr). We analysed the conservation of VSSC in both a broad scope and a narrow scope by three approaches: (1) we compared conservation of sequences and of differential exon use across orders of the Insecta; (2) we determined which kdr mutations were possible with a single nucleotide mutation in nine populations of Aedes aegypti; and (3) we examined the individual VSSC variation that exists within a population of Drosophila melanogaster. There is an increasing amount of transcript diversity possible from Diplura towards Diptera. The residues of the voltage sensors, selectivity filter and inactivation loop are highly conserved. The majority of exon sequences were >88.6% similar. Strain-specific differences in codon constraints exist for kdr mutations in nine strains of A. aegypti. Three Vssc mutations were found in one population of D. melanogaster. This study shows that, overall, Vssc is highly conserved across Insecta and within a population of an insect, but that important differences do exist.

Keywords: codon bias; insect; insecticide resistance; kdr; sodium channel evolution; voltage gated sodium channel.