Compensatory mechanisms in resistant Anopheles gambiae AcerKis and KdrKis neurons modulate insecticide-based mosquito control - Signalisation Fonctionnelle des Canaux Ioniques et Récepteurs Accéder directement au contenu
Article Dans Une Revue Communications Biology Année : 2021

Compensatory mechanisms in resistant Anopheles gambiae AcerKis and KdrKis neurons modulate insecticide-based mosquito control

Résumé

In the malaria vector Anopheles gambiae , two point mutations in the acetylcholinesterase ( ace-1 R ) and the sodium channel ( kdr R ) genes confer resistance to organophosphate/carbamate and pyrethroid insecticides, respectively. The mechanisms of compensation that recover the functional alterations associated with these mutations and their role in the modulation of insecticide efficacy are unknown. Using multidisciplinary approaches adapted to neurons isolated from resistant Anopheles gambiae AcerKis and KdrKis strains together with larval bioassays, we demonstrate that nAChRs, and the intracellular calcium concentration represent the key components of an adaptation strategy ensuring neuronal functions maintenance. In AcerKis neurons, the increased effect of acetylcholine related to the reduced acetylcholinesterase activity is compensated by expressing higher density of nAChRs permeable to calcium. In KdrKis neurons, changes in the biophysical properties of the L1014F mutant sodium channel, leading to enhance overlap between activation and inactivation relationships, diminish the resting membrane potential and reduce the fraction of calcium channels available involved in acetylcholine release. Together with the lower intracellular basal calcium concentration observed, these factors increase nAChRs sensitivity to maintain the effect of low concentration of acetylcholine. These results explain the opposite effects of the insecticide clothianidin observed in AcerKis and KdrKis neurons in vitro and in vivo.
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Dates et versions

hal-03341906 , version 1 (04-11-2021)

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Stéphane Perrier, Eléonore Moreau, Caroline Deshayes, Marine El-Adouzi, Delphine Goven, et al.. Compensatory mechanisms in resistant Anopheles gambiae AcerKis and KdrKis neurons modulate insecticide-based mosquito control. Communications Biology, 2021, 4, pp.1-16. ⟨10.1038/s42003-021-02192-0⟩. ⟨hal-03341906⟩
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