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TETRAMETHRIN AND DDT INHIBIT SPONTANEOUS FIRING IN CORTICAL NEURONAL NETWORKS
Citation:
Johnstone, A. F., A. Jay, AND T. J. SHAFER. TETRAMETHRIN AND DDT INHIBIT SPONTANEOUS FIRING IN CORTICAL NEURONAL NETWORKS. Presented at Society of Toxicology 49th Annual meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
These data demonstrate that tetramethrin and DDT alter network firing rates in a manner similar to other pyrethroids. In addition, these results expand our set of relative potency data for pyrethroids to 13 chemicals (including DDT), providing one of the largest comparisons of pyrethroid effects in mammalian neurons in vitro.
Description:
The insecticidal and neurotoxic effects of pyrethroids result from prolonged sodium channel inactivation, which causes alterations in neuronal firing and communication. Previously, we determined the relative potencies of 11 type I and type II pyrethroid insecticides using microelectrode array (MEA) recordings. In the present experiments, effects of the type I pyrethroid tetramethrin, or the organochlorine insecticide DDT, were examined on spontaneous spiking and bursting in primary cortical cultures on MEAs. DDT is an organochlorine insecticide that acts on voltage gated sodium channels in a manner similar to type I pyrethroids. We hypothesized that DDT's effects on network activity would be similar to pyrethroids. Effects of these compounds on spontaneous glutamatergic network spike and burst rates were determined by recording activity in the presence of blockers of GABA receptors. Spontaneous network spiking rate was inhibited by tetramethrin as well DDT, with IC50 values of 3252 and 358 nM, respectively. However, at the concentration closest to the IC5o, neither compound had significant effects on the number of bursts per minute, percent of spikes in bursts, burst duration or interspike interval. Thus, like other pyrethroids, tetramethrin and DDT alter network firing rates, but not the pattern of network bursting in glutamatergic networks. Tetramethrin was more potent than the least potent pyrethroid (resmethrin, IC50 = 16860 nM) examined to date, while DDT was similar in potency to the type II compound, p-cyfluthrin (IC5o = 305 nM). Tetramethrin and DDT were 0.054 and 0.489, respectively, as potent as deltamethrin (relative potency =1.0). These data demonstrate that tetramethrin and DDT alter network firing rates in a manner similar to other pyrethroids. In addition, these results expand our set of relative potency data for pyrethroids to 13 chemicals (including DDT), providing one of the largest comparisons of pyrethroid effects in mammalian neurons in vitro. (This is an abstract of a proposed presentation and does not necessarily reflect Agency Policy).