Block of two subtypes of sodium channels in cockroach neurons by indoxacarb insecticides

Xilong Zhao, Tomoko Ikeda, Vincent L. Salgado, Jay Z. Yeh, Toshio Narahashi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Indoxacarb, a novel insecticide, and its decarbomethoxyllated metabolite, DCJW, are known to block voltage-gated Na+ channels in insects and mammals, but the mechanism of block is not yet well understood. The present study was undertaken to characterize the action of indoxacarb and DCJW on cockroach Na+ channels. Na+ currents were recorded using the whole-cell patch clamp technique from neurons acutely dissociated from thoracic ganglia of the American cockroach Periplaneta americana L. Two types of tetrodotoxin-sensitive Na+ currents were observed, with different voltage dependencies of channel inactivation. Type-I Na+ currents were inactivated at more negative potentials than type-II Na+ currents. As a result, these two types of Na+ channels responded to indoxacarb compounds differentially. At a holding potential of -100 mV, type-I Na+ currents were inhibited reversibly by 1 μM indoxacarb and irreversibly by 1 μM DCJW in a voltage-dependent manner, whereas type-II Na+ currents were not affected by either of the compound. However, type-II Na+ currents were inhibited by indoxacarb or DCJW at more depolarizing membrane potentials, ranging from -60 to -40 mV. The slow inactivation curves of type-I and type-II Na+ channels were significantly shifted in the hyperpolarizing direction by indoxacarb and DCJW, suggesting that these compounds have high affinities for the inactivated state of the Na+ channels. It was concluded that the differential blocking actions of indoxacarb insecticides on type-I and type-II Na+ currents resulted from their different voltage dependence of Na+ channel inactivation. The irreversible nature of DCJW block may be partially responsible for its potent action in insects.

Original languageEnglish (US)
Pages (from-to)455-465
Number of pages11
JournalNeuroToxicology
Volume26
Issue number3
DOIs
StatePublished - Jun 2005

Keywords

  • Cockroach neuron
  • Indoxacarb
  • Insecticide
  • Pyrazoline
  • Sodium channel

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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