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Mutations in the transmembrane helix S6 of domain IV confer cockroach sodium channel resistance to sodium channel blocker insecticides and local anesthetics.

Publication ,  Journal Article
Jiang, D; Du, Y; Nomura, Y; Wang, X; Wu, Y; Zhorov, BS; Dong, K
Published in: Insect biochemistry and molecular biology
November 2015

Indoxacarb and metaflumizone are two sodium channel blocker insecticides (SCBIs). They preferably bind to and trap sodium channels in the slow-inactivated non-conducting state, a mode of action similar to that of local anesthetics (LAs). Recently, two sodium channel mutations, F1845Y (F(4i15)Y) and V1848I (V(4i18)I), in the transmembrane segment 6 of domain IV (IVS6), were identified to be associated with indoxacarb resistance in Plutella xylostella. F(4i15) is known to be critical for the action of LAs on mammalian sodium channels. Previously, mutation F(4i15)A in a cockroach sodium channel, BgNav1-1a, has been shown to reduce the action of lidocaine, a LA, but not the action of SCBIs. In this study, we introduced mutations F(4i15)Y and V(4i18)A/I individually into the cockroach sodium channel, BgNav1-1a, and conducted functional analysis of the three mutants in Xenopus oocytes. We found that both the F(4i15)Y and V(4i18)I mutations reduced the inhibition of sodium current by indoxacarb, DCJW (an active metabolite of indoxacarb) and metaflumizone. F(4i15)Y and V(4i18)I mutations also reduced the use-dependent block of sodium current by lidocaine. In contrast, substitution V(4i18)A enhanced the action metaflumizone and lidocaine. These results show that both F(4i15)Y and V(4i18)I mutations may contribute to target-site resistance to SCBIs, and provide the first molecular evidence for common amino acid determinants on insect sodium channels involved in action of SCBIs and LA.

Duke Scholars

Published In

Insect biochemistry and molecular biology

DOI

EISSN

1879-0240

ISSN

0965-1748

Publication Date

November 2015

Volume

66

Start / End Page

88 / 95

Related Subject Headings

  • Xenopus
  • Sodium Channels
  • Sodium Channel Blockers
  • Semicarbazones
  • Protein Domains
  • Oxazines
  • Oocytes
  • Mutation
  • Lidocaine
  • Insecticides
 

Citation

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ICMJE
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Jiang, D., Du, Y., Nomura, Y., Wang, X., Wu, Y., Zhorov, B. S., & Dong, K. (2015). Mutations in the transmembrane helix S6 of domain IV confer cockroach sodium channel resistance to sodium channel blocker insecticides and local anesthetics. Insect Biochemistry and Molecular Biology, 66, 88–95. https://doi.org/10.1016/j.ibmb.2015.09.011
Jiang, Dingxin, Yuzhe Du, Yoshiko Nomura, Xingliang Wang, Yidong Wu, Boris S. Zhorov, and Ke Dong. “Mutations in the transmembrane helix S6 of domain IV confer cockroach sodium channel resistance to sodium channel blocker insecticides and local anesthetics.Insect Biochemistry and Molecular Biology 66 (November 2015): 88–95. https://doi.org/10.1016/j.ibmb.2015.09.011.
Jiang D, Du Y, Nomura Y, Wang X, Wu Y, Zhorov BS, et al. Mutations in the transmembrane helix S6 of domain IV confer cockroach sodium channel resistance to sodium channel blocker insecticides and local anesthetics. Insect biochemistry and molecular biology. 2015 Nov;66:88–95.
Jiang, Dingxin, et al. “Mutations in the transmembrane helix S6 of domain IV confer cockroach sodium channel resistance to sodium channel blocker insecticides and local anesthetics.Insect Biochemistry and Molecular Biology, vol. 66, Nov. 2015, pp. 88–95. Epmc, doi:10.1016/j.ibmb.2015.09.011.
Jiang D, Du Y, Nomura Y, Wang X, Wu Y, Zhorov BS, Dong K. Mutations in the transmembrane helix S6 of domain IV confer cockroach sodium channel resistance to sodium channel blocker insecticides and local anesthetics. Insect biochemistry and molecular biology. 2015 Nov;66:88–95.

Published In

Insect biochemistry and molecular biology

DOI

EISSN

1879-0240

ISSN

0965-1748

Publication Date

November 2015

Volume

66

Start / End Page

88 / 95

Related Subject Headings

  • Xenopus
  • Sodium Channels
  • Sodium Channel Blockers
  • Semicarbazones
  • Protein Domains
  • Oxazines
  • Oocytes
  • Mutation
  • Lidocaine
  • Insecticides