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COMPLETE INHIBITION OF SPONTANEOUS ACTIVITY IN NEURONAL NETWORKS IN VITRO BY DELTAMETHRIN AND PERMETHRIN
Citation:
SHAFER, T. J., S. OLI, AND G. W. GROSS. COMPLETE INHIBITION OF SPONTANEOUS ACTIVITY IN NEURONAL NETWORKS IN VITRO BY DELTAMETHRIN AND PERMETHRIN. NEUROTOXICOLOGY. Intox Press, Inc, Little Rock, AR, 29(2):203-212, (2008).
Impact/Purpose:
These results demonstrate that both DM and PM inhibit activity of glutamatergic networks with a similar mode of action but with quantitative differences in potency.
Description:
Type I and II pyrethroid insecticides cause temporally distinct decreases in voltage-gated sodium channel (VGSC) inactivation rates that are proposed to underlie their characteristic differences in toxicity signs. How alterations in VGSC channel function give rise to the characteristic differences in signs of pyrethroid intoxication is not completely understood, particularly those changes that occur in networks of interconnected neurons. In order to characterize better the action of pyrethroid compounds at the network level, effects of the type I pyrethroid permethrin (PM) and the type II pyrethroid deltamethrin (DM) on spontaneous glutamate network-dependent spikes and bursts were investigated in primary cultures of cortical or spinal cord neurons grown on microelectrode arrays (MEAs). Based on previously reported effects in individual neurons, it was hypothesized that PM would increase spike and/or burst rates while DM would first increase, then decrease these measures. Fast GABAergic transmission was blocked by bicuculline (40 μM), and concentration-dependent effects of DM (1 nM - 5 μM) and PM (10 nM - 50 μM) were examined. Both compounds caused concentration-dependent reductions in the network spike and burst rates. DM was more potent than PM, with IC50 values of ~ 0.2 and ~4 μM for inhibition of spike rate in cortical and spinal cord neurons, respectively. Both compounds decreased the percentage of spikes that occurred within a burst and increased the interspike interval within bursts. Onset of effects was rapid, but recovery from total activity loss was not readily achievable. Contrary to the hypothesis, these results demonstrate that both DM and PM inhibit activity of glutamatergic networks with a similar mode of action but with quantitative differences in potency. Thus, differential actions on glutamatergic networks may not underlie the characteristic differences in signs of intoxication by Type I and II pyrethroids
