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Development of pharmacological and genetic tools to explore the potential of inward rectifier potassium channels as novel insecticide targets (654.9)
Author(s) -
Raphemot Rene,
EstevezLao Tania,
Rouhier Matthew,
Hillyer Julián,
Hopkins Corey,
Piermarini Peter,
Denton Jerod
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.654.9
Subject(s) - biology , potassium channel , rna interference , aedes aegypti , inward rectifier potassium ion channel , knockdown resistance , gene knockdown , computational biology , toxicology , genetics , ion channel , ecology , larva , pesticide , rna , pyrethroid , gene , cyfluthrin , receptor , biophysics
Inward rectifying potassium (Kir) channels play important physiological roles in humans and are expressed in various insect species such as mosquitoes. However, their potential as insecticidal targets remain largely unknown. Current chemical vector control strategies are becoming less effective due to the emergence of insecticide resistance. We have shown recently that impairment of Aedes aegypti Kir1 channels with a small molecule inhibitor elicits “renal failure” and death in culicine mosquitoes, and thus could represent a novel insecticidal target. We are employing medicinal chemistry to improve the potency and physicochemical properties of new Kir1 channel inhibitors identified via high‐throughput screening and assessing their effects on mosquito mortality. Quantitative RT‐PCR analyses revealed that Anopheles gambiae Kir1 is expressed in various tissues and is highest in the ovaries. To elucidate a putative role of Kir1 channels in anopheline mosquito reproduction, we developed a RNA interference strategy to knockdown Kir1 expression and assess its effects on mosquito fecundity. The use of these novel molecular and pharmacological tools will be useful to uncover novel physiological functions and the insecticidal potential of Kir channels in vectors of disease‐causing pathogens. Funded by a grant from the Foundation for the NIH, VCTR program.