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Distinct roles of the DmNav and DSC1 channels in the action of DDT and pyrethroids.

Publication ,  Journal Article
Rinkevich, FD; Du, Y; Tolinski, J; Ueda, A; Wu, C-F; Zhorov, BS; Dong, K
Published in: Neurotoxicology
March 2015

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 (para(ts)) 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 para(ts1) 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 para(ts1) mutant flies was almost completely abolished in para(ts1);DSC1(-/-) double mutant flies. Unexpectedly, however, the DSC1 knockout flies were less sensitive to DDT, compared to the control flies (w(1118A)), and the para(ts1);DSC1(-/-) double mutant flies were even more resistant to DDT compared to the DSC1 knockout or para(ts1) 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.

Duke Scholars

Published In

Neurotoxicology

DOI

EISSN

1872-9711

ISSN

0161-813X

Publication Date

March 2015

Volume

47

Start / End Page

99 / 106

Related Subject Headings

  • Xenopus
  • Toxicology
  • Sodium Channels
  • Pyrethrins
  • Oocytes
  • Mutation
  • Insecticides
  • Drosophila melanogaster
  • Drosophila Proteins
  • DDT
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Rinkevich, F. D., Du, Y., Tolinski, J., Ueda, A., Wu, C.-F., Zhorov, B. S., & Dong, K. (2015). Distinct roles of the DmNav and DSC1 channels in the action of DDT and pyrethroids. Neurotoxicology, 47, 99–106. https://doi.org/10.1016/j.neuro.2015.02.001
Rinkevich, Frank D., Yuzhe Du, Josh Tolinski, Atsushi Ueda, Chun-Fang Wu, Boris S. Zhorov, and Ke Dong. “Distinct roles of the DmNav and DSC1 channels in the action of DDT and pyrethroids.Neurotoxicology 47 (March 2015): 99–106. https://doi.org/10.1016/j.neuro.2015.02.001.
Rinkevich FD, Du Y, Tolinski J, Ueda A, Wu C-F, Zhorov BS, et al. Distinct roles of the DmNav and DSC1 channels in the action of DDT and pyrethroids. Neurotoxicology. 2015 Mar;47:99–106.
Rinkevich, Frank D., et al. “Distinct roles of the DmNav and DSC1 channels in the action of DDT and pyrethroids.Neurotoxicology, vol. 47, Mar. 2015, pp. 99–106. Epmc, doi:10.1016/j.neuro.2015.02.001.
Rinkevich FD, Du Y, Tolinski J, Ueda A, Wu C-F, Zhorov BS, Dong K. Distinct roles of the DmNav and DSC1 channels in the action of DDT and pyrethroids. Neurotoxicology. 2015 Mar;47:99–106.
Journal cover image

Published In

Neurotoxicology

DOI

EISSN

1872-9711

ISSN

0161-813X

Publication Date

March 2015

Volume

47

Start / End Page

99 / 106

Related Subject Headings

  • Xenopus
  • Toxicology
  • Sodium Channels
  • Pyrethrins
  • Oocytes
  • Mutation
  • Insecticides
  • Drosophila melanogaster
  • Drosophila Proteins
  • DDT