Eliciting Renal Failure in Mosquitoes with a Small-Molecule Inhibitor of Inward-Rectifying Potassium Channels

Rene Raphemot, Matthew F. Rouhier, Corey R. Hopkins, Rocco D. Gogliotti, Kimberly M. Lovell, Rebecca M. Hine, Dhairyasheel Ghosalkar, Anthony Longo, Klaus W. Beyenbach, Jerod S. Denton, Peter M. Piermarini

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Mosquito-borne diseases such as malaria and dengue fever take a large toll on global health. The primary chemical agents used for controlling mosquitoes are insecticides that target the nervous system. However, the emergence of resistance in mosquito populations is reducing the efficacy of available insecticides. The development of new insecticides is therefore urgent. Here we show that VU573, a small-molecule inhibitor of mammalian inward-rectifying potassium (Kir) channels, inhibits a Kir channel cloned from the renal (Malpighian) tubules of Aedes aegypti (AeKir1). Injection of VU573 into the hemolymph of adult female mosquitoes (Ae. aegypti) disrupts the production and excretion of urine in a manner consistent with channel block of AeKir1 and renders the mosquitoes incapacitated (flightless or dead) within 24 hours. Moreover, the toxicity of VU573 in mosquitoes (Ae. aegypti) is exacerbated when hemolymph potassium levels are elevated, suggesting that Kir channels are essential for maintenance of whole-animal potassium homeostasis. Our study demonstrates that renal failure is a promising mechanism of action for killing mosquitoes, and motivates the discovery of selective small-molecule inhibitors of mosquito Kir channels for use as insecticides.

Original languageEnglish (US)
Article numbere64905
JournalPloS one
Volume8
Issue number5
DOIs
StatePublished - May 29 2013

Fingerprint

Potassium Channels
potassium channels
renal failure
Insecticides
Culicidae
Renal Insufficiency
Potassium
Molecules
insecticides
Aedes aegypti
Hemolymph
Neurology
hemolymph
Toxicity
potassium
mosquito-borne diseases
Animals
Health
Malpighian Tubules
Malpighian tubules

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Raphemot, R., Rouhier, M. F., Hopkins, C. R., Gogliotti, R. D., Lovell, K. M., Hine, R. M., ... Piermarini, P. M. (2013). Eliciting Renal Failure in Mosquitoes with a Small-Molecule Inhibitor of Inward-Rectifying Potassium Channels. PloS one, 8(5), [e64905]. https://doi.org/10.1371/journal.pone.0064905

Eliciting Renal Failure in Mosquitoes with a Small-Molecule Inhibitor of Inward-Rectifying Potassium Channels. / Raphemot, Rene; Rouhier, Matthew F.; Hopkins, Corey R.; Gogliotti, Rocco D.; Lovell, Kimberly M.; Hine, Rebecca M.; Ghosalkar, Dhairyasheel; Longo, Anthony; Beyenbach, Klaus W.; Denton, Jerod S.; Piermarini, Peter M.

In: PloS one, Vol. 8, No. 5, e64905, 29.05.2013.

Research output: Contribution to journalArticle

Raphemot, R, Rouhier, MF, Hopkins, CR, Gogliotti, RD, Lovell, KM, Hine, RM, Ghosalkar, D, Longo, A, Beyenbach, KW, Denton, JS & Piermarini, PM 2013, 'Eliciting Renal Failure in Mosquitoes with a Small-Molecule Inhibitor of Inward-Rectifying Potassium Channels', PloS one, vol. 8, no. 5, e64905. https://doi.org/10.1371/journal.pone.0064905
Raphemot, Rene ; Rouhier, Matthew F. ; Hopkins, Corey R. ; Gogliotti, Rocco D. ; Lovell, Kimberly M. ; Hine, Rebecca M. ; Ghosalkar, Dhairyasheel ; Longo, Anthony ; Beyenbach, Klaus W. ; Denton, Jerod S. ; Piermarini, Peter M. / Eliciting Renal Failure in Mosquitoes with a Small-Molecule Inhibitor of Inward-Rectifying Potassium Channels. In: PloS one. 2013 ; Vol. 8, No. 5.
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