Ginsburg K S, Narahashi T
Department of Pharmacology, Northwestern University Medical School, Chicago, IL 60611.
Brain Res. 1993 Nov 12;627(2):239-48. doi: 10.1016/0006-8993(93)90326-i.
The pyrethroid insecticides are known to modify neuronal sodium channels to cause a prolongation of whole cell current. The sodium channels expressed in the dorsal root ganglion neurons of the rat are of two types, one highly sensitive to tetrodotoxin and the other highly resistant to tetrodotoxin. The pyrethroid allethrin exerted profound effects on tetrodotoxin-resistant sodium channels while causing minimal effects on tetrodotoxin-sensitive sodium channels. Currents derived from tetrodotoxin-resistant sodium channels were greatly prolonged during a step depolarization; the tail currents upon repolarization were also augmented and prolonged. In the tetrodotoxin-sensitive sodium channel currents, these changes caused by allethrin were much smaller or negligible. The activation and inactivation voltages of tetrodotoxin-resistant peak sodium currents were not significantly altered by allethrin. The differential action of allethrin on the two types of sodium channels would be important not only in identifying the target molecular structure but also in interpreting the symptoms of poisoning in mammals.
已知拟除虫菊酯类杀虫剂可改变神经元钠通道,导致全细胞电流延长。大鼠背根神经节神经元中表达的钠通道有两种类型,一种对河豚毒素高度敏感,另一种对河豚毒素高度耐药。拟除虫菊酯类的丙烯菊酯对河豚毒素耐药性钠通道有显著影响,而对河豚毒素敏感性钠通道影响极小。在阶跃去极化过程中,来自河豚毒素耐药性钠通道的电流大幅延长;复极化时的尾电流也增强并延长。在河豚毒素敏感性钠通道电流中,丙烯菊酯引起的这些变化要小得多或可忽略不计。丙烯菊酯对河豚毒素耐药性峰值钠电流的激活和失活电压没有显著改变。丙烯菊酯对两种类型钠通道的差异作用不仅在确定靶分子结构方面很重要,而且在解释哺乳动物中毒症状方面也很重要。