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Relative potencies of Type I and Type II pyrethroids for inhibition of spontaneous firing in neuronal networks.
Citation:
LOSA, S., A. F. JOHNSTONE, AND T. J. SHAFER. Relative potencies of Type I and Type II pyrethroids for inhibition of spontaneous firing in neuronal networks. Presented at Annual meeting of the Society of Toxicology, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
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Description:
Pyrethroids insecticides commonly used in pest control disrupt the normal function of voltage-sensitive sodium channels. We have previously demonstrated that permethrin (a Type I pyrethroid) and deltamethrin (a Type II pyrethroid) inhibit sodium channel-dependent spontaneous network activity of rat cortical neurons in vitro; both compounds had similar effects. The current study further compared effects of Type I and II pyrethroids by characterizing the concentration-response of inhibition of spontaneous activity by β-cyfluthrin, cypermethrin and λ-cyhalothrin (Type II), as well as bifenthrin, teflutrin, S-bioallethrin and resmethrin (Type I), and fenpropathrin (mixed type). Primary cultures of rat cortical neurons from postnatal day 1-2 pups were grown on multiple electrode arrays. After 10-30 days in vitro, spontaneous network activity consisting of individual spikes and bursts developed and stabilized. Concentration-dependent effects of pyrethroids (1nM to 50 µM) on spontaneous network activity were determined in the presence of 10µM biccuculine and 20µM SCH50911 (to inhibit gabaergic input). All 11 compounds caused a concentration-dependent decrease in mean network spike rates. λ-Cyhalothrin was the most potent compound, with an IC50 of 25 nM, while S¬-bioallethrin fenpropathrin and resmethrin were the least potent, with IC50 values of ~1.5 uM. Using deltamethrin as the index chemical, relative potencies ranged from 0.12 to 7.0. In general, Type II compounds were more potent than the Type I compounds or fenpropathrin. A mixture of 5 compounds (permethin, cypermethrin cyfluthrin deltamethrin and esfenvalerate) similarly decreased spontaneous spike rate in a manner that was not effect additive. These data demonstrate that demonstrate that Type I and Type II pyrethroids inhibit network activity in a similar manner. Whether pyrethroid effects are dose-additive is currently being examined. (This is an abstract of a proposed presentation and does not necessarily reflect Agency Policy)