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DELTAMETHRIN AND PERMETHRIN DECREASE SPONTANEOUS NETWORK ACTIVITY IN VITRO.
Citation:
RIJAL, J. O., G. W. GROSS, AND T. J. SHAFER. DELTAMETHRIN AND PERMETHRIN DECREASE SPONTANEOUS NETWORK ACTIVITY IN VITRO. Presented at Society of Toxicology, San Diego, CA, March 05 - 09, 2006.
Description:
ABSTRACT BODY: Pyrethroid insecticides alter inactivation of voltage-sensitive sodium channels, an action that underlies their insecticidal and neurotoxicological properties. How alterations in sodium channel function give rise to the characteristic signs of pyrethroid intoxication are not completely understood, particularly those changes that occur in networks of interconnected neurons. Therefore, pyrethroid effects on spontaneous electrical activity in primary cultures of cortical or spinal cord neurons grown on microelectrode arrays were investigated. . Concentration-dependent effects of deltamethrin (1 nM - 5 M) and permethrin (10 nM - 50 M) were examined after blocking fast GABAergic transmission with 40 M icuculline. Pyrthroids were added to the cells in culture medium containing 5 and 10 % serum for cortical and spinal cord cultures, respectively. Both compounds caused a concentration-dependent reduction in spike frequency (#spikes/min), as well as burst frequency (#bursts/min). Deltamethrin was more potent than permethrin, with respective IC50 values of ~200 nM and ~4 M for spike frequency inhibition in both tissues (n = 3-5). Onset of effects was rapid and not readily reversible, although effects could be partially reversed with successive complete medium replacements. Although mean network activity decreased, individual unit responses were heterogeneous; ~25 and 9% of units treated with deltamethrin and permethrin, respectively, responded with biphasic (increasing, then decreasing) changes in spike frequency. The balance of units responded with only decreases in activity. These results demonstrate that both deltamethrin and permethrin inhibit network activity in cortical and spinal cord cultures in vitro, and suggest that despite differences in the clinical signs of poisoning, similar modes of action at the network level may contribute to effects of these compounds. (This abstract does not necessarily reflect EPA policy. Mention of trade names or products does not constitute endorsement)