Mechanisms of pyrethroid insecticide-induced stimulation of calcium influx in neocortical neurons.

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Cao Z, Shafer TJ, Murray TF

Mechanisms of pyrethroid insecticide-induced stimulation of calcium influx in neocortical neurons.

J Pharmacol Exp Ther. 2011 Jan;336(1):197-205. doi: 10.1124/jpet.110.171850. Epub 2010 Sep 29.

PubMed ID

20881019 [ View in PubMed

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Abstract

Pyrethroid insecticides bind to voltage-gated sodium channels (VGSCs) and modify their gating kinetics, thereby disrupting neuronal function. Pyrethroids have also been reported to alter the function of other channel types, including activation of voltage-gated calcium channels. Therefore, the present study compared the ability of 11 structurally diverse pyrethroids to evoke Ca(2+) influx in primary cultures of mouse neocortical neurons. Nine pyrethroids (tefluthrin, deltamethrin, lambda-cyhalothrin, beta-cyfluthrin, esfenvalerate, S-bioallethrin, fenpropathrin, cypermethrin, and bifenthrin) produced concentration-dependent elevations in intracellular calcium concentration ([Ca(2+)](i)) in neocortical neurons. Permethrin and resmethrin were without effect on [Ca(2+)](i). These pyrethroids displayed a range of efficacies on Ca(2+) influx; however, the EC(50) values for active pyrethroids all were within one order of magnitude. Tetrodotoxin blocked increases in [Ca(2+)](i) caused by all nine active pyrethroids, indicating that the effects depended on VGSC activation. The pathways for deltamethrin- and tefluthrin-induced Ca(2+) influx include N-methyl-D-aspartic acid receptors, L-type Ca(2+) channels, and reverse mode of operation of the Na(+)/Ca(2+) exchanger inasmuch as antagonists of these sites blocked deltamethrin-induced Ca(2+) influx. These data demonstrate that pyrethroids stimulate Ca(2+) entry into neurons subsequent to their actions on VGSCs.

DrugBank Data that Cites this Article

Drugs

Bioallethrin

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Bioallethrin	Voltage-dependent calcium channel (Protein Group)	Protein group	Humans	Unknown	Agonist	Details
Permethrin	Sodium channel protein type 1 subunit alpha	Protein	Humans	Yes	Inhibitor	Details