当前位置： SCI文献检索 > TOXICOLOGY AND APPLIED PHARMACOLOGY期刊下所有文献 > Divergent actions of the pyrethroid insecticides S-bioallethrin, tefluthrin, and deltamethrin on rat Na(v)1.6 sodium channels.

Divergent actions of the pyrethroid insecticides S-bioallethrin, tefluthrin, and deltamethrin on rat Na(v)1.6 sodium channels.

Abstract：

:We expressed rat Na(v)1.6 sodium channels in combination with the rat beta(1) and beta(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 microM), 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 ~9-fold more persistent than those caused by S-bioallethrin, barely detectable resting modification (2.5% modification at 100 microM), 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 microM), 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 approximately 15-fold and that tefluthrin was approximately 10-fold more potent than deltamethrin as a use-dependent modifier of Na(v)1.6 sodium channels. Concentration-effect data from parallel experiments with the rat Na(v)1.2 sodium channel coexpressed with the rat beta(1) and beta(2) subunits in oocytes showed that the Na(v)1.6 isoform was at least 15-fold more sensitive to tefluthrin and deltamethrin than the Na(v)1.2 isoform. These results implicate sodium channels containing the Na(v)1.6 isoform as potential targets for the central neurotoxic effects of pyrethroids.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Tan J,Soderlund DM

doi

10.1016/j.taap.2010.07.001

subject

Has Abstract

pub_date

2010-09-15 00:00:00

pages

229-37

issue

3

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(10)00227-9

journal_volume

247

pub_type

杂志文章

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