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

Abstract

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 on Anopheles 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. Topical treatments with LD10 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 of Periplaneta americana giant axons, 2S (10μm) and 4-AP (30 μm) caused multiple spikes after a single stimulation. Permethrin at 10μm showed significant summating depolarization (4.5 ± 1.1mV) after a train of ten stimuli were applied at 5Hz, and deltamethrin at 0.03 μm showed significant membrane depolarization of 2.9± 0.4mV without stimuli. 2S at 0.3μm and 4-AP at 1-3μm significantly synergized the effects of 3μm permethrin and 0.01 μm deltamethrin. Co-application of potassium channel blockers 2S and 4-AP with pyrethroids can synergize the mosquitocidal activities on An.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. © 2020 Society of Chemical Industry.