Fatty acid and related potassium Kv2 channel blockers: toxicity and physiological actions on mosquitoes

Authors: DEMARES, FABIEN - University Of Florida; COQUEREL, QUENTIN - University Of Florida; RICHOUX, GARY - University Of Florida; Linthicum, Kenneth - Ken; BLOOMQUIST, JEFFREY - University Of Florida

Submitted to: Insects
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/30/2018
Publication Date: 11/1/2018
Citation: Demares, F., Coquerel, Q., Richoux, G., Linthicum, K., Bloomquist, J. 2018. Fatty acid and related potassium Kv2 channel blockers: toxicity and physiological actions on mosquitoes. Insects. 9(4):1-12. https://doi.org/10.3390/insects9040155.
DOI: https://doi.org/10.3390/insects9040155

Interpretive Summary: Ion channels are important macromolecular structures and are major actors in osmotic balance and cell signaling. Polyunsaturated fatty acids can block potassium channels and voltage-gated channels of mosquitoes could represent interesting targets for developing new pesticide compounds. In this work, we tested fatty acid compounds as potential insecticides against Anopheles gambiae larval and adult mosquitoes. Insecticidal activity was assessed by topical application on Anopheles gambiae adult female mosquitoes and preparations of larvae, and at the cellular level with patch-clamp recordings on engineered HEK cells expressing AgKv2.1 channels. The compounds tested had modest insecticidal and synergistic activity when combined with the insecticide permethrin.

Technical Abstract: Potassium channels constitute a very diverse group involved in neural signaling, neuronal activity, membrane potential maintenance, and action potential generation. Here, we tested compounds potassium channel blockers, such as TRAM-34 or 5-hydroxydecanoate (5-HDC), as well as fatty acids (FA), which might fit in the lumen of the pore and block the channel activity by obstructing K+ ion passage. As possible Kv channel blockers, these compounds could represent a lead for a novel pesticide type. Insecticidal activity was assessed by topical application on Anopheles gambiae adult female mosquitoes and insect preparations, and at the cellular level with patch-clamp recordings on engineered HEK cells expressing AgKv2.1 channels. With only one hydroxyl group difference, decanoate had a consistently greater effect than 5-HDC in blocking Kv channels, paralyzing larvae, and killing adult mosquitoes. We showed the effect of DAUDA blocking the activity of eukaryotic Kv channels for the first time, but it failed to kill adult mosquitoes. We synthesized methyl esters from DAUDA and methyl decanoate in an effort to improve cuticular penetration, but it had little effect 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.