Editors' ChoiceToxicology

Too stimulated to suck

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Sci. Signal.  19 May 2015:
Vol. 8, Issue 377, pp. ec129
DOI: 10.1126/scisignal.aac5766

Many insecticides target an insect’s nervous system. Pymetrozine (PM) and pyrifluquinazon (PFQ) disrupt the function of sensory cells called chordotonal neurons that control body movement in flies. PM and PFQ kill plant-sucking insects, like aphids, by impairing mouth movement, so the insects cannot eat. Nesterov et al. used the fruitfly Drosophila to investigate the specific molecular targets of PM and PFQ, because in these insects the chemicals are not lethal and impair gravity sensing and hearing instead of feeding. PM and PFQ placed in the drinking water caused inactivity, impaired anti-gravitaxis (their usual desire to walk up against the gravitational field), and abolished sound-induced antennal responses in wild-type Drosophila but not those lacking Nanchung (Nan) or Inactive (Iav), two vanilloid subfamily members of transient receptor potential (TRP) cation channels that mediate neuronal activity in response to various sensations. Fluorescent reporters revealed that Nan and Iav formed a complex exclusively in the sensory chordotonal neurons. Application of PM or PFQ induced Ca2+ signals only in this type of sensory neuron and only in the subset that were positive for both Nan and Iav. However, compound action potentials in the cells were rapidly silenced soon after exposure to PM and PFQ, indicating electrical silencing through overstimulation. Transfection experiments in Chinese hamster ovary (CHO) cells confirmed heteromeric complex formation between Drosophila Nan and Iav and their ability to mediate PM- or PFQ-induced Ca2+ responses. Application of a cell-impermeable TRP inhibitor or removal of extracellular Ca2+ blocked PM- or PFQ-induced Ca2+ responses in CHO cells coexpressing Nan and Iav. A fluorescent voltage indicator revealed changes in the cell membrane potential after PM or PFQ exposure, indicating that the Nan/Iav TRP channel complex stimulated Ca2+ influx at the plasma membrane rather than release of Ca2+ from internal stores. The findings suggested that, although the physiological role of these channels differs between fruit flies and the targeted insects, activation of this TRP channel complex may be the molecular mechanism of action of these insecticides.

A. Nesterov, C. Spalthoff, R. Kandasamy, R. Katana, N. B. Rankl, M. Andrés, P. Jähde, J. A. Dorsch, L. F. Stam, F. -J. Braun, B. Warren, V. L. Salgado, M. C. Göpfert, TRP channels in insect stretch receptors as insecticide targets. Neuron 86, 665–671 (2015). [PubMed]