Location: Mosquito and Fly ResearchTitle: Fatty acids and related Kv2 channel blockers: electrophysiology and toxicity on mosquitoes Author
|Demares, Fabien - University Of Florida|
|Coquerel, Quentin - University Of Florida|
|Richoux, Gary - University Of Florida|
|Linthicum, Kenneth - Ken|
|Bernier, Ulrich - Uli|
|Bloomquist, Jeffrey - University Of Florida|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 2/2/2018
Publication Date: 2/15/2018
Citation: Demares, F.J., Coquerel, Q.R., Richoux, G.M., Linthicum, K., Bernier, U.R., Bloomquist, J.R. 2018. Fatty acids and related Kv2 channel blockers: electrophysiology and toxicity on mosquitoes. Meeting Abstract. pg. 1.
Technical Abstract: Ligand-gated ion channels form an important superfamily of proteins involved in many biological processes. Among them, the potassium channels constitute a very diverse group involved in neural signaling, neuronal activity and action potential. Among the different types of channel activation, voltage-gated potassium channels (Kv) are sensitive to membrane polarization. In their structure, they possess a voltage-sensor domain (subunits S1 to S4) and a selectivity filter inside the pore (subunits 5 and 6); the assembly of four subunits will form a channel. In this work, we tested diverse compounds that were reported as potassium channel blockers, such as TRAM-34 or 5-Hydroxydecanoate (5-HDC) (Wang et al. 2007, Notsu et al. 1992) but their effects have not been explored on voltage-gated Kv channels. Other compounds such as fatty acids (FA), due to their structures, might fit in the lumen of the pore and block the channel activity. To test this hypothesis, we performed patch-clamp recordings of engineered HEK cells expressing Kv2.1 channels. As possible Kv channel blockers, these compounds could represent a lead for novel pesticides. Thus, we tested these compounds for insecticidal effects through topical application on adult mosquitoes (Anopheles gambiae and Aedes aegypti), and through insect preparations (An. gambiae intact and headless larvae assay and Drosophila central nervous system recordings). Electrophysiological recordings revealed that fatty acid compounds without groups on the main chain (e.g. Decanoate, DAUDA) yield a more potent action on Kv2.1 currents than fatty acids with long-chain groups (e.g. 5-HDC, a hydroxy group in position 5 in the chain). Also, in comparison to PRC1358, a known Kv channel blocker, decanoate and DAUDA yield a similar potential to block potassium current in vivo. Results obtained through headless larvae assays were very similar to those obtained through patch-clamp recordings. It indicates a continuum between cell level and organ/organism level. Yet, when these compounds (DAUDA and decanoate) were tested on adult mosquitoes, even though they knocked down insects, they were not as lethal as PRC1358. One possible reason for this difference is compound penetration through the mosquito cuticle. To solve this, we are currently working on new non-polar compounds that could short-circuit the cuticle barrier. The other potential K+ channel blockers, namely TRAM-34 and Rolipram, did not yield any promising effect on mosquitoes.