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Binary Mixtures of Pyrethroids Interact with Voltage-Sensitive Calcium and Chloride Channels in Isolated Presynaptic Nerve Terminals from Rat Brain

Hilliary E. Hodgdon, University of Massachusetts-Amherst

Document Type: Open Access

Degree Program

Animal Science

Degree Type

Master of Science (M.S.)

Year Degree Awarded

2008

Month Degree Awarded

September

Primary Subject Category

Toxicology

Secondary Subject Category

Veterinary science

Keywords

Pyrethroids, VGCC, VGClC, Synaptosomes, Rat Brain

Advisor(s) or Committee Chair

Clark, John M.

 

Abstract

Select pyrethroid binary mixtures (deltamethrin plus <em>S</em>-bioallethrin, β-cyfluthrin, cypermethrin, and fenpropathrin) elicit a more-than-additive response on L-glutamate release from rat brain synaptosomes that is independent of calcium influx. Using a variety of chloride channel antagonists, anthracene-9-carboxylic acid (9-AC), rChlorotoxin (ClTx), 4,4’-dintitrostilbene-2,2’-disulfonic acid (DNDS), 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), and picrotoxinin (PTX), we have identified two mechanisms by which pyrethroids may enhance L-glutamate release. The results from this study indicate that only ClTx and NPPB, at their EC<sub>50</sub>s (0.1 μM and 70 μM, respectively), significantly increase L-glutamate release when in the presence of our most potent pyrethroid, deltamethrin, at its EC<sub>50</sub> (2 x 10<sup>-12</sup> M). When these two antagonists were used in the presence of deltamethrin plus cypermethrin and deltamethrin plus fenpropathrin, a more-than-additive response was elicited at lower concentrations of the binary mixtures. Likewise, NPPB in the presence of the additive binary mixture, deltamethrin plus tefluthrin, first elicited a more-than-additive response at the 1:10 mixture. Since both ClTx and NPPB are inhibitors of voltage-gated chloride channels (ClC-2) and calcium-activated chloride channels, our findings suggest that these channels are potential target sites for certain pyrethroids and likely are important in pyrethroid neurotoxicity.

Recommended Citation

Hodgdon, Hilliary E., "Binary Mixtures of Pyrethroids Interact with Voltage-Sensitive Calcium and Chloride Channels in Isolated Presynaptic Nerve Terminals from Rat Brain" (2008). Masters Theses. Paper 201.
http://scholarworks.umass.edu/theses/201