Neurotoxic implications of the agonistic action of CS-syndrome pyrethroids on the N-type Cav2.2 calcium channel

摘要: BACKGROUND: Cismethrin (T-syndrome) and deltamethrin (CS-syndrome) pyrethroids have been previously shown to increase membrane depolarization calcium influx, but only increased Ca2+-dependent neurotransmitter release from rat brain synaptosomes. Deltamethrin's action was blocked by ω-conotoxin GVIA, delineating a separate at N-type Cav2.2 channels that is consistent with the in vivo of neurotransmitter. It hypothesized other CS-syndrome will elicit similar actions presynaptic nerve terminals. RESULTS: Nine additional were similarly examined, these data used cluster analysis. possessed α-cyano groups, cypermethrin, esfenvalerate, all caused Ca2+ influx clustered two pyrethroids, cyfluthrin cyhalothrin, shared same actions. T-syndrome bioallethrin, cismethrin fenpropathrin, did not share non-α-cyano tefluthin bifenthrin, which likewise Deltamethrin reduced peak current heterologously expressed wild-type Cav2.2, T422E 20-fold more potent on than channels, indicating permanently phosphorylated form preferred target. CONCLUSIONS: directly modified deltamethrin, resulting perturbation dependent upon its phosphorylation state. The present findings may provide partial explanation for different toxic syndromes produced structurally distinct pyrethroids. Copyright © 2008 Society Chemical Industry