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

Zhengyu Cao, Timothy J. Shafer, Thomas F. Murray

Research output: Contribution to journalArticle

57 Citations (Scopus)

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, λ-cyhalothrin, β-cyfluthrin, esfenvalerate, S-bioallethrin, fenpropathrin, cypermethrin, and bifenthrin) produced concentration-dependent elevations in intracellular calcium concentration ([Ca2+]i) in neocortical neurons. Permethrin and resmethrin were without effect on [Ca2+]i. These pyrethroids displayed a range of efficacies on Ca2+ influx; however, the EC 50 values for active pyrethroids all were within one order of magnitude. Tetrodotoxin blocked increases in [Ca2+]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 +/Ca2+ exchanger inasmuch as antagonists of these sites blocked deltamethrin-induced Ca2+ influx. These data demonstrate that pyrethroids stimulate Ca2+ entry into neurons subsequent to their actions on VGSCs.

Original languageEnglish
Pages (from-to)197-205
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume336
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

Pyrethrins
Insecticides
Calcium
Neurons
Voltage-Gated Sodium Channels
fenpropathrin
fenvalerate
Permethrin
Tetrodotoxin
N-Methylaspartate
Calcium Channels

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Molecular Medicine

Cite this

Mechanisms of pyrethroid insecticide-induced stimulation of calcium influx in neocortical neurons. / Cao, Zhengyu; Shafer, Timothy J.; Murray, Thomas F.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 336, No. 1, 01.2011, p. 197-205.

Research output: Contribution to journalArticle

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