Eliciting renal failure in mosquitoes with a small-molecule inhibitor of inward-rectifying potassium channels

Autor: Rebecca M. Hine, Rocco D. Gogliotti, Peter M. Piermarini, Jerod S. Denton, Rene Raphemot, Dhairyasheel Ghosalkar, Klaus W. Beyenbach, Anthony Longo, Matthew F. Rouhier, Corey R. Hopkins, Kimberly M. Lovell
Rok vydání: 2013
Předmět:
0106 biological sciences
Insecticides
Patch-Clamp Techniques
Anatomy and Physiology
lcsh:Medicine
Pharmacology
01 natural sciences
Mosquitoes
Dengue fever
Membrane Potentials
Aedes
Hemolymph
Integrative Physiology
Drug Discovery
lcsh:Science
0303 health sciences
Multidisciplinary
Molecular Structure
Potassium channel
3. Good health
Electrophysiology
Culex
Chemistry
Infectious Diseases
Insect Proteins
Medicine
Female
Imines
medicine.symptom
Research Article
medicine.medical_specialty
Cell Physiology
Drugs and Devices
Drug Research and Development
Aedes aegypti
Biology
Malpighian Tubules
03 medical and health sciences
Internal medicine
parasitic diseases
Anopheles
medicine
Potassium Channel Blockers
Animals
Humans
Animal Physiology
Patch clamp
Potassium Channels
Inwardly Rectifying
030304 developmental biology
Renal Physiology
Dose-Response Relationship
Drug
lcsh:R
fungi
Vectors and Hosts
Renal System
medicine.disease
biology.organism_classification
010602 entomology
Endocrinology
HEK293 Cells
Mechanism of action
Potassium
lcsh:Q
Benzimidazoles
Fluid Physiology
Medicinal Chemistry
Zoology
Entomology
Malaria
Homeostasis
Zdroj: PLoS ONE
PLoS ONE, Vol 8, Iss 5, p e64905 (2013)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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