科研之友
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摘要
We expressed rat Na(v)1.6 sodium channels in combination with the rat beta(1) and beta(2) auxiliary subunits in Xeno pus 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 similar to 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 similar to 15-fold and that tefluthrin was similar to 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.
- 出版日期2010-9-15
