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Influence of Pyrethroid Insecticides on Sodium and Calcium Influx in Neocortical Neurons
Citation:
CAO, Z., T. J. SHAFER, AND T. F. MURRAY. Influence of Pyrethroid Insecticides on Sodium and Calcium Influx in Neocortical Neurons. Presented at Annual Meeting of the Society of Toxicology, Baltimore, MD, March 15 - 19, 2009.
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Description:
Pyrethroid insecticides bind to voltage-gated sodium channels and modify their gating kinetics, thereby disrupting neuronal function. Using murine neocortical neurons in primary culture, we have compared the ability of 11 structurally diverse pyrethroid insecticides to evoke Na+ and Ca2+ influx. Nine pyrethroid insecticides including telfluthrin, deltamethrin, lambda-cyhalothrin, beta-cyfluthrin, esfenvalerate, s-bioallethrin, fenpropathrin, cyperthrin and biofenthrin produced concentration-dependant elevations of intracellular Na+ and Ca2+ in neocortical neurons. Two of the 11 pyrethroids tested, resmethrin and permethrin, did not produce Na+ or Ca2+ influx. The EC50 values for the 9 active pyrethroids on Na+ influx ranged from 1.44 M (deltamethrin) to 5.86 M (fenpropathrin). The corresponding potencies on Ca2+ influx for these pyrethroids varied from 1.93 M (ensfenvarate) to 11.9 M (tefluthrin). Pyrethroid efficacies for both Na+ and Ca2+ influx were all lower than that of veratridine. Tefluthrin was the most efficacious pyrethroid insectide as demonstrated by an increment of [Na+]i greater than 20 mM. Biofenthrin was a low efficacy pyrethroid producing an increase of [Na+]i less than 3 mM. The rank order of efficacy of the 9 pyrethroids in the Na+ influx assay was telfluthrin> deltamethrin> lambda-cyhalothrin> beta-cyfluthrin> esfenvalerate> s-bioallethrin> fenpropathrin> cyperthrin> biofenthrin. Similarly, pyrethroid insecticide-induced Ca2+ influx also displayed distinct efficacies. The rank order of efficacy on Ca2+ influx was deltamethrin> telfluthrin> lamda-cyhalothrin> beta-cyfluthrin> esfenvalerate> fenpropathrin> cyperthrin > biofenthrin> s-bioallethrin. Considered together, these data suggest that the most salient differences between pyrethroids on Na+ and Ca2+ influx were in their respective efficacies rather than potencies. Additionally assessment of the influence of pyrethroid mixtures on Na+ influx revealed predictable additive effects. These data indicate that monitoring of pyrethroid effects on neocortical neuron [Na+]i using the fluorescent dye SBFI is a useful assay for comparison of pyrethroid efficacies.