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A negative charge in transmembrane segment 1 of domain II of the cockroach sodium channel is critical for channel gating and action of pyrethroid insecticides.

Publication ,  Journal Article
Du, Y; Song, W; Groome, JR; Nomura, Y; Luo, N; Dong, K
Published in: Toxicology and applied pharmacology
August 2010

Voltage-gated sodium channels are the primary target of pyrethroids, an important class of synthetic insecticides. Pyrethroids bind to a distinct receptor site on sodium channels and prolong the open state by inhibiting channel deactivation and inactivation. Recent studies have begun to reveal sodium channel residues important for pyrethroid binding. However, how pyrethroid binding leads to inhibition of sodium channel deactivation and inactivation remains elusive. In this study, we show that a negatively charged aspartic acid residue at position 802 (D802) located in the extracellular end of transmembrane segment 1 of domain II (IIS1) is critical for both the action of pyrethroids and the voltage dependence of channel activation. Charge-reversing or -neutralizing substitutions (K, G, or A) of D802 shifted the voltage dependence of activation in the depolarizing direction and reduced channel sensitivity to deltamethrin, a pyrethroid insecticide. The charge-reversing mutation D802K also accelerated open-state deactivation, which may have counteracted the inhibition of sodium channel deactivation by deltamethrin. In contrast, the D802G substitution slowed open-state deactivation, suggesting an additional mechanism for neutralizing the action of deltamethrin. Importantly, Schild analysis showed that D802 is not involved in pyrethroid binding. Thus, we have identified a sodium channel residue that is critical for regulating the action of pyrethroids on the sodium channel without affecting the receptor site of pyrethroids.

Duke Scholars

Published In

Toxicology and applied pharmacology

DOI

EISSN

1096-0333

ISSN

0041-008X

Publication Date

August 2010

Volume

247

Issue

1

Start / End Page

53 / 59

Related Subject Headings

  • Toxicology
  • Sodium Channels
  • Pyrethrins
  • Protein Structure, Tertiary
  • Nitriles
  • Membrane Potentials
  • Ion Channel Gating
  • Insecticides
  • Cockroaches
  • Aspartic Acid
 

Citation

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MLA
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Du, Y., Song, W., Groome, J. R., Nomura, Y., Luo, N., & Dong, K. (2010). A negative charge in transmembrane segment 1 of domain II of the cockroach sodium channel is critical for channel gating and action of pyrethroid insecticides. Toxicology and Applied Pharmacology, 247(1), 53–59. https://doi.org/10.1016/j.taap.2010.05.016
Du, Yuzhe, Weizhong Song, James R. Groome, Yoshiko Nomura, Ningguang Luo, and Ke Dong. “A negative charge in transmembrane segment 1 of domain II of the cockroach sodium channel is critical for channel gating and action of pyrethroid insecticides.Toxicology and Applied Pharmacology 247, no. 1 (August 2010): 53–59. https://doi.org/10.1016/j.taap.2010.05.016.
Du Y, Song W, Groome JR, Nomura Y, Luo N, Dong K. A negative charge in transmembrane segment 1 of domain II of the cockroach sodium channel is critical for channel gating and action of pyrethroid insecticides. Toxicology and applied pharmacology. 2010 Aug;247(1):53–9.
Du, Yuzhe, et al. “A negative charge in transmembrane segment 1 of domain II of the cockroach sodium channel is critical for channel gating and action of pyrethroid insecticides.Toxicology and Applied Pharmacology, vol. 247, no. 1, Aug. 2010, pp. 53–59. Epmc, doi:10.1016/j.taap.2010.05.016.
Du Y, Song W, Groome JR, Nomura Y, Luo N, Dong K. A negative charge in transmembrane segment 1 of domain II of the cockroach sodium channel is critical for channel gating and action of pyrethroid insecticides. Toxicology and applied pharmacology. 2010 Aug;247(1):53–59.
Journal cover image

Published In

Toxicology and applied pharmacology

DOI

EISSN

1096-0333

ISSN

0041-008X

Publication Date

August 2010

Volume

247

Issue

1

Start / End Page

53 / 59

Related Subject Headings

  • Toxicology
  • Sodium Channels
  • Pyrethrins
  • Protein Structure, Tertiary
  • Nitriles
  • Membrane Potentials
  • Ion Channel Gating
  • Insecticides
  • Cockroaches
  • Aspartic Acid