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) |
|---|---|
| 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 |
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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
Cite this
Time course and temperature dependence of allethrin modulation of sodium channels in rat dorsal root ganglion cells. / Ginsburg, Kenneth S; Narahashi, Toshio.
In: Brain Research, Vol. 847, No. 1, 13.11.1999, p. 38-49.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Time course and temperature dependence of allethrin modulation of sodium channels in rat dorsal root ganglion cells
AU - Ginsburg, Kenneth S
AU - Narahashi, Toshio
PY - 1999/11/13
Y1 - 1999/11/13
N2 - 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.
AB - 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.
KW - Allethrin
KW - Dorsal root ganglion neuron
KW - Tail current
KW - Temperature effect
KW - Tetrodotoxin-resistant sodium channel
KW - Tetrodotoxin-sensitive sodium channel
UR - http://www.scopus.com/inward/record.url?scp=0032728107&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032728107&partnerID=8YFLogxK
U2 - 10.1016/S0006-8993(99)02029-6
DO - 10.1016/S0006-8993(99)02029-6
M3 - Article
C2 - 10564734
AN - SCOPUS:0032728107
VL - 847
SP - 38
EP - 49
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1
ER -