Characterization of Caenorhabditis elegans transient receptor potential vanilloid (TRPV) channels and their interactions with insecticidal compounds

Abstract

A number of insecticidal compounds have been found to affect the insect transient receptor potential vanilloid (TRPV) channel. As this receptor is also found in nematodes, we investigated whether these compounds could also interact with the Caenorhabditis elegans TRPV channel in order to explore the possibility of leveraging this target for nematicide development. Here we report on the characterization of C. elegans TRPV channels using electrophysiology and radioligand binding. Evidence of channel activation is demonstrated for OSM9:OCR1, OSM9:OCR2, and OSM9:OCR4 with the natural agonist, nicotinamide. Additionally, insecticides (pymetrozine and pyrifluquinazon – IRAC group 9) known to be insect TRPV agonists were evaluated for nematode TRPV channel modulation. While activation of the nematode channel was not observed, a novel antagonistic blocking effect was discovered. Specificity of this modulation is confirmed by testing the active metabolite (4-trifluoromethylnicotinamide) of a different class of insecticide, flonicamid(IRAC group 29), known to be a non-TRPV chordotonal modulator. We also report competitive binding data for nicotinamide (Ki = 0.13 μM), pymetrozine (Ki = 0.51 μM), and pyrifluquinazon (Ki = 27.3 μM) with [³H]-nicotinamide, demonstrating that they are likely to share a binding pocket on the TRPV channel. These data suggest TRPV may also be a novel target for nematicide development.