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Pharmacological Inhibition of Inward Rectifier Potassium Channels Induces Lethality in Larval Aedes aegypti

1
Department of Entomology, The Ohio State University, Ohio Agricultural Research and Development Center, Wooster, OH 44691, USA
2
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA
3
Departments of Anesthesiology and Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
*
Author to whom correspondence should be addressed.
Insects 2018, 9(4), 163; https://doi.org/10.3390/insects9040163
Received: 15 October 2018 / Revised: 7 November 2018 / Accepted: 12 November 2018 / Published: 15 November 2018
(This article belongs to the Special Issue Integrative Mosquito Biology: From Molecules to Ecosystems)
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Abstract

The inward rectifier potassium (Kir) channels play key roles in the physiology of mosquitoes and other insects. Our group, among others, previously demonstrated that small molecule inhibitors of Kir channels are promising lead molecules for developing new insecticides to control adult female mosquitoes. However, the potential use of Kir channel inhibitors as larvicidal agents is unknown. Here we tested the hypothesis that pharmacological inhibition of Kir channels in the larvae of Aedes aegypti, the vector of several medically important arboviruses, induces lethality. We demonstrated that adding barium, a non-specific blocker of Kir channels, or VU041, a specific small-molecule inhibitor of mosquito Kir1 channels, to the rearing water (deionized H2O) of first instar larvae killed them within 48 h. We further showed that the toxic efficacy of VU041 within 24 h was significantly enhanced by increasing the osmolality of the rearing water to 100 mOsm/kg H2O with NaCl, KCl or mannitol; KCl provided the strongest enhancement compared to NaCl and mannitol. These data suggest: (1) the important role of Kir channels in the acclimation of larvae to elevated ambient osmolality and KCl concentrations; and (2) the disruption of osmoregulation as a potential mechanism of the toxic action of VU041. The present study provides the first evidence that inhibition of Kir channels is lethal to larval mosquitoes and broadens the potential applications of our existing arsenal of small molecule inhibitors of Kir channels, which have previously only been considered for developing adulticides. View Full-Text
Keywords: mosquito; Kir channel; barium; VU041; small molecule; insecticide mosquito; Kir channel; barium; VU041; small molecule; insecticide
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Rusconi Trigueros, R.; Hopkins, C.R.; Denton, J.S.; Piermarini, P.M. Pharmacological Inhibition of Inward Rectifier Potassium Channels Induces Lethality in Larval Aedes aegypti. Insects 2018, 9, 163.

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