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The Promise of Microelectrode Array Approaches for Toxicity Testing: Examples with Neuroactive Chemicals
Citation:
JOHNSTONE, A. F. AND T. J. SHAFER. The Promise of Microelectrode Array Approaches for Toxicity Testing: Examples with Neuroactive Chemicals. Presented at Society of Toxicology Annual Meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
We have used MEAs to determine relative potencies of DDT and twelve different pyrethroids (insecticides that alter sodium channel function), as well as effects of pyrethroid mixtures.
Description:
While high-throughput patch clamping formats provide rapid characterization of chemical effects on ion channel function and kinetics, the limitations of such systems often include the need for channel by channel characterization, requirements for transfected, rather than primary cells, and the inability to assess effects on spatial and temporal functions ofnetworks ofcells. Microelectrode Arrays (MEAs) allow recordings from primary neurons or cardiomyocytes, and provide information derived from individual sites as well as spatial and temporal information. Because the function of the cell rather than a specific ion channel is measured, drug or chemical actions at any site affecting electrical activity ofthe cell may be detected, an advantage when screening chemicals where no information exists regarding the potential mode of action. The pattern of activity changes can be used to provide information regarding the site of action (i.e. channel) for a chemical. MEAs have been used to examine a wide variety ofdrugs and chemicals, including those acting on GABAA receptors, sodium channels, calcium channels and other sites oftoxicological interest. We have used MEAs to determine relative potencies of DDT and twelve different pyrethroids (insecticides that alter sodium channel function), as well as effects of pyrethroid mixtures. The MEA relative potency values for pyrethroids are consistent with those determined from in vivo studies. Currently, we are examining actions of other classes of drugs and chemicals including fluoxetine (a selective 5-HT reuptake inhibitor), muscimol (a GABAA R agonist), and verapamil (a calcium channel blocker) as part of a multi-lab study to determine reproducibility ofdata across labs and MEA platforms. These examples will be used to discuss both the advantages as well as the limitations ofMEA approaches for predictive toxicity testing. (This abstract does not reflect EPA policy).