Modulation of tetrodotoxin-resistant sodium channels by dihydropyrazole insecticide RH-3421 in rat dorsal root ganglion neurons

Yuji Tsurubuchi, Xilong Zhao, Keiichi Nagata, Yoshiaki Kono, Keiichiro Nishimura, Jay Z. Yeh, Toshio Narahashi

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The effects of the dihydropyrazole insecticide RH-3421 on the tetrodotoxin-resistant (TTX-R) voltage-gated sodium channels in rat dorsal root ganglion (DRG) neurons were studied using the whole-cell patch clamp technique. RH-3421 at 10 nM to 1 μM completely blocked action potentials. The sodium currents were irreversibly suppressed by 1 μM RH-3421 in a time- and a dose-dependent manner and the IC50 value of RH-3421 was estimated to be 0.7 μM after 10 min of application. RH-3421 blocked the sodium currents to the same extent over the entire range of test potentials. The sodium conductance-voltage curve was not shifted along the voltage axis by 1 μM RH-3421 application. In contrast, both fast and slow steady-state sodium channel inactivation curves were shifted in the hyperpolarizing direction in the presence of 1 μM RH-3421. It was concluded that RH-3421 bound to the resting and inactivated sodium channels to cause block with a higher affinity for the latter state.

Original languageEnglish (US)
Pages (from-to)743-753
Number of pages11
JournalNeuroToxicology
Volume22
Issue number6
DOIs
StatePublished - 2001

Keywords

  • Dihydropyrazole
  • Dorsal root ganglion
  • RH-3421
  • Sodium channel
  • Tetrodotoxin-resistant sodium channel

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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