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 language | English (US) |
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Pages (from-to) | 38-49 |
Number of pages | 12 |
Journal | Brain Research |
Volume | 847 |
Issue number | 1 |
DOIs | |
State | Published - Nov 13 1999 |
Externally published | Yes |
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