Skip to main content
Journal cover image

Role of the sixth transmembrane segment of domain IV of the cockroach sodium channel in the action of sodium channel blocker insecticides.

Publication ,  Journal Article
Silver, KS; Nomura, Y; Salgado, VL; Dong, K
Published in: Neurotoxicology
July 2009

Sodium channel blocker insecticides (SCBIs), such as indoxacarb and metaflumizone, are a new class of insecticides with a mechanism of action different from those of other insecticides that target sodium channels. SCBIs block sodium channels in a manner similar to local anesthetics (LAs) such as lidocaine. Several residues, particularly F1579 and Y1586, in the sixth transmembrane segment (S6) of domain IV (IV) of rat Na(v)1.4 sodium channels are required for the action of LAs and SCBIs and may form part of overlapping receptor sites. However, the binding site for SCBIs in insect sodium channels remains undefined. We used site-directed mutagenesis, the Xenopus laevis oocyte expression system, and the two-electrode voltage clamp technique to study the effects on SCBI activity of mutating F1817 and Y1824 (analogous to those residues identified in mammalian sodium channels) to alanine, in the voltage-sensitive sodium channel of the German cockroach, Blattella germanica. The mutant channels showed no effect or a marked increase in channel sensitivity to both DCJW (the active metabolite of indoxacarb) and metaflumizone. Thus, it appeared that although the F1817 residue plays a role in the action of SCBIs and that both residues are involved in LA activity in mammalian sodium channels, neither F1817 nor Y1824 are integral determinants of SCBI binding on insect sodium channels. Our results suggest that the receptor site of SCBIs on insect sodium channels may be significantly different from that on mammalian sodium channels.

Duke Scholars

Published In

Neurotoxicology

DOI

EISSN

1872-9711

ISSN

0161-813X

Publication Date

July 2009

Volume

30

Issue

4

Start / End Page

613 / 621

Related Subject Headings

  • Xenopus laevis
  • Tyrosine
  • Toxicology
  • Time Factors
  • Sodium Channel Blockers
  • Semicarbazones
  • Protein Structure, Tertiary
  • Phenylalanine
  • Patch-Clamp Techniques
  • Oxazines
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Silver, K. S., Nomura, Y., Salgado, V. L., & Dong, K. (2009). Role of the sixth transmembrane segment of domain IV of the cockroach sodium channel in the action of sodium channel blocker insecticides. Neurotoxicology, 30(4), 613–621. https://doi.org/10.1016/j.neuro.2009.03.009
Silver, Kristopher S., Yoshiko Nomura, Vincent L. Salgado, and Ke Dong. “Role of the sixth transmembrane segment of domain IV of the cockroach sodium channel in the action of sodium channel blocker insecticides.Neurotoxicology 30, no. 4 (July 2009): 613–21. https://doi.org/10.1016/j.neuro.2009.03.009.
Silver, Kristopher S., et al. “Role of the sixth transmembrane segment of domain IV of the cockroach sodium channel in the action of sodium channel blocker insecticides.Neurotoxicology, vol. 30, no. 4, July 2009, pp. 613–21. Epmc, doi:10.1016/j.neuro.2009.03.009.
Journal cover image

Published In

Neurotoxicology

DOI

EISSN

1872-9711

ISSN

0161-813X

Publication Date

July 2009

Volume

30

Issue

4

Start / End Page

613 / 621

Related Subject Headings

  • Xenopus laevis
  • Tyrosine
  • Toxicology
  • Time Factors
  • Sodium Channel Blockers
  • Semicarbazones
  • Protein Structure, Tertiary
  • Phenylalanine
  • Patch-Clamp Techniques
  • Oxazines