Journal article
Distinct roles of the DmNav and DSC1 channels in the action of DDT and pyrethroids
Neurotoxicology (Park Forest South), Vol.47, pp.99-106
03/2015
DOI: 10.1016/j.neuro.2015.02.001
PMCID: PMC4486006
PMID: 25687544
Abstract
•The I265N mutation in the parats1 allele is responsible for resistance to DDT and pyrethroids.•DSC1 knockout (DSC1−/−) flies are resistant to DDT, but more sensitive to pyrethroids.•parats1;DSC1−/− double mutant flies are more resistant to DDT than DSC1−/− flies.•Pyrethroid resistance in parats1 mutant flies was almost completely abolished in parats1;DSC1−/− double mutant flies.
Voltage-gated sodium channels (Nav channels) are critical for electrical signaling in the nervous system and are the primary targets of the insecticides DDT and pyrethroids. In Drosophila melanogaster, besides the canonical Nav channel, Para (also called DmNav), there is a sodium channel-like cation channel called DSC1 (Drosophila sodium channel 1). Temperature-sensitive paralytic mutations in DmNav (parats) confer resistance to DDT and pyrethroids, whereas DSC1 knockout flies exhibit enhanced sensitivity to pyrethroids. To further define the roles and interaction of DmNav and DSC1 channels in DDT and pyrethroid neurotoxicology, we generated a DmNav/DSC1 double mutant line by introducing a parats1 allele (carrying the I265N mutation) into a DSC1 knockout line. We confirmed that the I265N mutation reduced the sensitivity to two pyrethroids, permethrin and deltamethrin of a DmNav variant expressed in Xenopus oocytes. Computer modeling predicts that the I265N mutation confers pyrethroid resistance by allosterically altering the second pyrethroid receptor site on the DmNav channel. Furthermore, we found that I265N-mediated pyrethroid resistance in parats1 mutant flies was almost completely abolished in parats1;DSC1−/− double mutant flies. Unexpectedly, however, the DSC1 knockout flies were less sensitive to DDT, compared to the control flies (w1118A), and the parats1;DSC1−/− double mutant flies were even more resistant to DDT compared to the DSC1 knockout or parats1 mutant. Our findings revealed distinct roles of the DmNav and DSC1 channels in the neurotoxicology of DDT vs. pyrethroids and implicate the exciting possibility of using DSC1 channel blockers or modifiers in the management of pyrethroid resistance.
Details
- Title: Subtitle
- Distinct roles of the DmNav and DSC1 channels in the action of DDT and pyrethroids
- Creators
- Frank D Rinkevich - Department of Entomology, Michigan State University, East Lansing, MI 48824, United StatesYuzhe Du - Department of Entomology, Michigan State University, East Lansing, MI 48824, United StatesJosh Tolinski - Department of Entomology, Michigan State University, East Lansing, MI 48824, United StatesAtsushi Ueda - Department of Biology, University of Iowa, Iowa City, IA 52242, United StatesChun-Fang Wu - Department of Biology, University of Iowa, Iowa City, IA 52242, United StatesBoris S Zhorov - Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, CanadaKe Dong - Department of Entomology, Michigan State University, East Lansing, MI 48824, United States
- Resource Type
- Journal article
- Publication Details
- Neurotoxicology (Park Forest South), Vol.47, pp.99-106
- DOI
- 10.1016/j.neuro.2015.02.001
- PMID
- 25687544
- PMCID
- PMC4486006
- NLM abbreviation
- Neurotoxicology
- ISSN
- 0161-813X
- eISSN
- 1872-9711
- Publisher
- Elsevier B.V
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: GM080255, GM057445
- Language
- English
- Date published
- 03/2015
- Academic Unit
- Iowa Neuroscience Institute; Biology
- Record Identifier
- 9984070889502771
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