Time course and temperature dependence of allethrin modulation of sodium channels in rat dorsal root ganglion cells

Kenneth S Ginsburg, Toshio Narahashi

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Key effects of the pyrethroid insecticide allethrin, delivered to or washed out from cells at 10 or 100 μM in 0.1% DMSO, on neuronal Na+ channel currents were studied in rat dorsal root ganglion (DRG) cells under whole-cell patch clamp. Tetrodotoxin-resistant (TTX-R) Na+ channels were more responsive to allethrin than tetrodotoxin-sensitive (TTX-S) Na+ channels. On application of 10 or 100 μM allethrin to cells with TTX-R Na+ channels, the Na+ tail current during repolarization developed a large slowly decaying component within 10 min. This slow tail developed multiphasically, suggesting that allethrin gains access to Na+ channels by a multiorder process. On washout (with 0.1% DMSO present), the slow tail current disappeared monophasically (exponential τ=188±44 s). Development and washout rates did not depend systematically on temperature (12°, 18°, or 27°C), but washout was slowed severely if DMSO was absent. As the duration of a depolarizing pulse was increased (range 0.32-10 ms), the amplitude of the slow component of the succeeding tail conductance first increased then decreased. Tail current amplitude had the same dependence on preceding pulse duration (at 18°) at 10 or 100 μM, consistent with allethrin modification of Na+ channels at rest before opening. At 10 μM, slow tail conductance was at maximum 40% of the peak conductance during the previous depolarization, independent of temperature; evidently, the fraction of open modified channels did not change. However, at low temperature, the tail is more prolonged, bringing more Na+ ions into a cell. In functioning neurons, this Na+ influx would cause a larger depolarizing afterpotential, a condition favoring the repetitive discharges, which are signatory of pyrethroid intoxication. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)38-49
Number of pages12
JournalBrain Research
Volume847
Issue number1
DOIs
StatePublished - Nov 13 1999
Externally publishedYes

Keywords

  • Allethrin
  • Dorsal root ganglion neuron
  • Tail current
  • Temperature effect
  • Tetrodotoxin-resistant sodium channel
  • Tetrodotoxin-sensitive sodium channel

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Developmental Biology
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Time course and temperature dependence of allethrin modulation of sodium channels in rat dorsal root ganglion cells'. Together they form a unique fingerprint.

  • Cite this