Abstract
Potassium channels constitute a very diverse group involved in neural signaling, neuronal activity, membrane potential maintenance, and action potential generation. Here, we tested the mammalian potassium channel blockers TRAM-34 and 5-hydroxydecanoate (5-HDC), as well as certain fatty acids (FA) that might fit in the lumen of the pore and block channel activity by obstructing K+ ion passage. Kv channel blockers could be leads for a novel pesticide type. Insecticidal activity was assessed by topical application to Anopheles gambiae adult mosquitoes, paralysis in a headless larval assay, at the cellular level with patch-clamp recordings of engineered HEK cells expressing AgKv2.1 channels, as well as central nervous system recordings from larval Drosophila melanogaster. With only one hydroxyl group difference, decanoic acid had a consistently greater effect than 5-HDC in blocking Kv channels, paralyzing larvae, and killing mosquitoes. The 11-dansylamino undecanoic acid (DAUDA) blockage of eukaryotic Kv channels is demonstrated for the first time, but it failed to kill adult mosquitoes. We synthesized alkyl esters from DAUDA and decanoic acid in an effort to improve cuticular penetration, but it had little impact upon adult toxicity. TRAM-34 and rolipram did not show activity on Kv channels nor potent insecticidal effect on adult mosquitoes. Furthermore, co-application of test compounds with permethrin did not increase mortality in adults. In conclusion, the compounds tested had modest insecticidal and synergistic activity.
Highlights
The ion channels are important macromolecular structures and are major actors in osmotic balance and cell signaling
The 11-dansylamino undecanoic acid (DAUDA) blockage of eukaryotic Kv channels is demonstrated for the first time, but it failed to kill adult mosquitoes
Mosquitoes were reared to adulthood from Anopheles gambiae eggs collected from an insecticidesusceptible G3 (MRA112) strain obtained from the CDC (Atlanta, GA, USA)
Summary
The ion channels are important macromolecular structures and are major actors in osmotic balance and cell signaling. It has been previously established that (a) polyunsaturated fatty acids (FA) can block delayedrectifier potassium channels [10,11], and that (b) voltage-gated Kv2 channels of mosquitoes could represent interesting targets for developing new pesticidal compounds [12,13]. These compounds have been tested as putative insecticides Another strategy to improve the insecticidal activity of the compounds is to look at the synergistic effect with a common pyrethroid, permethrin. Channel blockers as permethrin synergists for control of disease-vectoring mosquitoes In light of these results, we discuss the use of fatty acids as biochemicals in the scope of integrated pest management, to better fit the legislative framework of pesticides regulation [27]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
