Divergent actions of the pyrethroid insecticides S-bioallethrin, tefluthrin, and deltamethrin on rat Na{sub v}1.6 sodium channels
We expressed rat Na{sub v}1.6 sodium channels in combination with the rat {beta}{sub 1} and {beta}{sub 2} auxiliary subunits in Xenopus laevis oocytes and evaluated the effects of the pyrethroid insecticides S-bioallethrin, deltamethrin, and tefluthrin on expressed sodium currents using the two-electrode voltage clamp technique. S-Bioallethrin, a type I structure, produced transient modification evident in the induction of rapidly decaying sodium tail currents, weak resting modification (5.7% modification at 100 {mu}M), and no further enhancement of modification upon repetitive activation by high-frequency trains of depolarizing pulses. By contrast deltamethrin, a type II structure, produced sodium tail currents that were {approx} 9-fold more persistent than those caused by S-bioallethrin, barely detectable resting modification (2.5% modification at 100 {mu}M), and 3.7-fold enhancement of modification upon repetitive activation. Tefluthrin, a type I structure with high mammalian toxicity, exhibited properties intermediate between S-bioallethrin and deltamethrin: intermediate tail current decay kinetics, much greater resting modification (14.1% at 100 {mu}M), and 2.8-fold enhancement of resting modification upon repetitive activation. Comparison of concentration-effect data showed that repetitive depolarization increased the potency of tefluthrin {approx} 15-fold and that tefluthrin was {approx} 10-fold more potent than deltamethrin as a use-dependent modifier of Na{sub v}1.6 sodium channels. Concentration-effect data from parallel experiments with the rat Na{sub v}1.2 sodium channel coexpressed with the rat {beta}{sub 1} and {beta}{sub 2} subunits in oocytes showed that the Na{sub v}1.6 isoform was at least 15-fold more sensitive to tefluthrin and deltamethrin than the Na{sub v}1.2 isoform. These results implicate sodium channels containing the Na{sub v}1.6 isoform as potential targets for the central neurotoxic effects of pyrethroids.
- OSTI ID:
- 21438067
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 247, Issue 3; Other Information: DOI: 10.1016/j.taap.2010.07.001; PII: S0041-008X(10)00227-9; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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