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Pyrethroid action on calcium channels: neurotoxicological implications

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Invertebrate Neuroscience

Abstract

Actions of cismethrin versus deltamethrin were compared using two functional attributes of rat brain synaptosomes. Both pyrethroids increased calcium influx but only deltamethrin increased Ca2+-dependent neurotransmitter release following K+-stimulated depolarization. The action of deltamethrin was stereospecific, concentration-dependent, and blocked by ω-conotoxin GVIA. These findings delineate a separate action for deltamethrin and implicate N-type rat brain Cav2.2 voltage-sensitive calcium channels (VSCC) as target sites that are consistent with the in vivo release of neurotransmitter caused by deltamethrin. Deltamethrin (10−7 M) reduced the peak current (approx. −47%) of heterologously expressed wild type Cav2.2 in a stereospecific manner. Mutation of threonine 422 to glutamic acid (T422E) in the α1-subunit results in a channel that functions as if it were permanently phosphorylated. Deltamethrin now increased peak current (approx. +49%) of T422E Cav2.2 in a stereospecific manner. Collectively, these results substantiate that Cav2.2 is directly modified by deltamethrin but the resulting perturbation is dependent upon the phosphorylation state of Cav2.2. Our findings may provide a partial explanation for the different toxic syndromes produced by these structurally-distinct pyrethroids.

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Acknowledgments

We thank Dr. Diana Lipscombe (Brown University, Providence, RI) for providing us the Cav2.2 subunits (α−1B-d and β3). We thank the Pyrethroid Working Group (PWG: Adventis CropSci., Bayer Corp., DuPont Ag. Prod., FMC Corp., Valent USA Corp., and Syngenta) for providing the pyrethroids used in this study. Partial support For S. Symington was provided by RI-INBRE (NIH/NCRR. #P20PR016457).

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  1. Department of Veterinary and Animal Science, University of Massachusetts, Morrill 1 N311, 639 N. Pleasant St., Amherst, MA, 01003, USA

    J. Marshall Clark

  2. Department of Biology and Biomedical Science, Salve Regina University, Newport, RI, 02840, USA

    Steven B. Symington

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  1. J. Marshall Clark
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Correspondence to J. Marshall Clark.

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Clark, J.M., Symington, S.B. Pyrethroid action on calcium channels: neurotoxicological implications. Invert Neurosci 7, 3–16 (2007). https://doi.org/10.1007/s10158-006-0038-7

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