Synergistic effects of potassium channel blockers and pyrethroids: mosquitocidal activity and neuronal mode of action†

BACKGROUND The purpose of this research was to explore the possibility of co-applying pyrethroids (agonists of voltage-sensitive sodium channels) with potassium channel blockers in order to potentiate the neurological effects of pyrethroids onAnopheles gambiae. We hypothesized that the toxicity of pyrethroids caused by persistent sodium currents would be augmented by blockage of outward potassium current flow, which normally repolarizes the membrane potential during a nerve membrane action potential. RESULTS Topical treatments with LD(10)s (10% mortality doses) of synergists were given with pyrethroids. 2S-65465 (2S) showed the best synergism of permethrin (8.6-fold) and deltamethrin (7.2-fold), whereas piperonyl butoxide and 4-aminopyridine only showed 2.2- to 3.4-fold synergism with these pyrethroids. In electrophysiological recordings ofPeriplaneta americanagiant axons, 2S (10 mu m) and 4-AP (30 mu m) caused multiple spikes after a single stimulation. Permethrin at 10 mu mshowed significant summating depolarization (4.5 +/- 1.1 mV) after a train of ten stimuli were applied at 5 Hz, and deltamethrin at 0.03 mu mshowed significant membrane depolarization of 2.9 +/- 0.4 mV without stimuli. 2S at 0.3 mu mand 4-AP at 1-3 mu msignificantly synergized the effects of 3 mu mpermethrin and 0.01 mu mdeltamethrin. CONCLUSIONS Co-application of potassium channel blockers 2S and 4-AP with pyrethroids can synergize the mosquitocidal activities onAn. gambiae, and these activities are correlated with synergistic effects at the level of the nerve membrane. If deployed in the field, this approach can potentially reduce the amount of chemicals needed for effective control of mosquitoes.