Enhanced pyrethroid potency in Drosophila melanogaster expressing voltage-gated potassium channel mutants:...

Previous studies have shown that blockers of voltage-gated potassium (Kv) channels, such as 4-aminopyridine (4-AP) and 2-methoxy-N-((1-phenylcyclopentyl)methyl)benzamide (2-MPB) synergized pyrethroid toxicity as well, or better than, piperonyl butoxide. The present study assessed the involvement of different Kv channels as possible pyrethroid synergist targets in Drosophila melanogaster. Three Kv1 mutants (Sh⁵, Sh¹³³, and Sh^M) and one Kv2 mutant (Shab³) were tested. All Kv1 mutant flies showed increased sensitivity to permethrin in topical and glass contact toxicity assays, of 2- to 11-fold. Central nervous system (CNS) recordings of larval D. melanogaster showed a similar pattern of increased sensitivity. Potentiated effects were also observed with deltamethrin on the mutants Sh⁵ (30- to 35-fold) and Sh¹³³ (33- to 47-fold), but the mutant Sh^M showed little change in sensitivity. In contrast, the Shab³ strain showed toxicity and physiological effects of both pyrethroids that were similar to the susceptible OR strain. Thus, some K⁺ channel mutations mimicked the synergistic effect of channel blockers. Additional studies showed that Shab³ had the highest sensitivity to 4-AP in topical assays, and the Shaker-null mutants, Sh^M and Sh¹³³ showed greater sensitivity to 2-MPB in CNS recordings of larval D. melanogaster. These results suggest that Kv1 channels are a useful synergist target for pyrethroids, as assessed both in whole insects and at the level of the nervous system. Thus, Kv1-targeting compounds can potentially serve as insect control tools to reduce pyrethroid use via synergistic action.