A Drosophila mutation that reduces sodium channel number confers resistance to pyrethroid insecticides

Abstract

The no action potential, temperature-sensitive (nap^ts) mutation in Drosophila melanogaster confers resistance to the pyrethroids fenvalerate and permethrin. Additionally we have found that females are more resistant to pyrethroids than males. Piperonyl butoxide can suppress this resistance in a long pyrethroid exposure (>45 min) but has less of an effect during shorter exposures. Since the pyrethroid resistance of nap^ts can be suppressed by piperonyl butoxide, the nap mutant appears to define a phenotypically different locus than the kdr mutant in house flies. Previous work has demonstrated that the nap^ts mutation decreases the number of saxitoxin-binding sodium channels. We propose that the presence of fewer sodium channels in mutant flies delays knockdown by pyrethroids, which act as channel agonists. This delay allows other mechanisms to come into play which, in turn, allow survivial. This model is supported by the finding that the nap resistance can be mimicked by feeding wild-type flies a sublethal dose of tetrodotoxin to reduce the number of functional channels. Although the nap^ts mutation is resistant to sodium channel agonists, the same single gene mutation causes enhanced sensitivity to the sodium channel antagonist, tetrodotoxin. These observations suggest that an effective way to deal with this form of hereditary insecticide resistance might be to simultaneously administer a sodium channel antagonist, along with the pyrethroid. However, our results illustrate a difficulty with such an approach. We demonstrate that sublethal doses of a channel antagonist cause "pharmacological" resistance to pyrethroids even in wild-type strains.