Differential sensitivity of Drosophila voltage-gated sodium channel variants to pyrethroid insecticides

Voltage-gated sodium channels are the primary target of pyrethroids, a large class of synthetic insecticides. Pyrethroids inhibit both inactivation and deactivation of sodium channels, resulting in prolonged opening of sodium channels. In the past decade, numerous studies have been carried out to uncover sodium channel residues that are involved in the action of pyrethroids on sodium channels. However, our understanding of how pyrethroids modulate sodium channel gating remains incomplete. In this study, we examined the sensitivity of 30 Drosophila sodium channel variants to two pyrethroids, deltamethrin and permethrin. We identified several variants that are highly resistant or highly sensitive to deltamethrin and/or permethrin. Site-directed mutagenesis is being performed to determine which residues are responsible for the differential pyrethroid-sensitivity. Understanding how these variants respond to pyrethroids differently should shed light on the molecular mechanism by which pyrethroids modulate sodium channel gating.