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Type I and Type II Pyrethroid alterations in Spontaneous Bursting Parameters in Rat Cortical Networks measured Using Multielectrode Array Recordings
Citation:
JOHNSTONE, A. F., S. LOSA, AND T. J. SHAFER. Type I and Type II Pyrethroid alterations in Spontaneous Bursting Parameters in Rat Cortical Networks measured Using Multielectrode Array Recordings. Presented at Annual meeting of the Society Toxicology, Baltimore, MD, March 15 - 19, 2009.
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Description:
Pyrethroids are widely used in agricultural, industrial and residential settings to control insect pests. Pyrethroids prolong sodium channel inactivation, although their complete mode of action is not fully understood. We previously reported that permethrin (a Type I pyrethroid) and deltamethrin (a Type II pyrethroid) disrupt bursting characteristics of rat hippocampal neurons in vitro by increasing the interspike interval (ISI) and decreasing the burst duration (BD). Here, we utilize cortical neurons grown on multielectrode arrays to analyze effects of 5 pyrethroid compounds [permethrin (P), cypermethrin (Cy), β-cyfluthrin (βC), deltamethrin (D) and esfenvalerate (Esf)] on spontaneous network burst characteristics. Effects of approximate IC50 concentrations for decreases in spontaneous spike rate of each compound on bursts per minute (BPM), % of spikes occurring within a burst (%SB), BD and ISI were determined. In addition, effects of a mixture of these compounds (52.2% P, 28.8% Cy, 12.9% BC, 3.4% D and 2.7% Esf; 2.68 µg/mL total pyrethroid) on burst parameters were also examined. Individually, Cy (100 nM) significantly decreased BPM by 52.3% (p=0.03), and Esf (1000 nM) significantly decreased %SB by 45.6% (p=0.05) and increased ISI by 17.7% (p=0.01) compared to control (defined as bursting activity in the presence of the GABAergic blockers bicuculline, 10uM and SCH50911, 20uM). Individually, D (100 nM), P (1000 nM) and βC (500 nM) did not significantly alter any burst parameter. In the mixture, both %SB and BD were significantly reduced by 49.6% (p=0.01) and 61.6% (p=0.01), respectfully. These data demonstrate that individual pyrethroids alter burst characteristics of cortical neuronal networks individually as well as in mixtures. Whether these effects are dose-additive or effect additive is currently being examined. (This is an abstract of a proposed presentation and does not necessarily reflect Agency Policy).