Ruigt G S, Neyt H C, Van der Zalm J M, Van den Bercken J
Department of Veterinary Pharmacology, Pharmacy and Toxicology, University of Utrecht, The Netherlands.
Brain Res. 1987 Dec 29;437(2):309-22. doi: 10.1016/0006-8993(87)91645-3.
The effects of 4 different pyrethroid insecticides on sodium channel gating in internally perfused, cultured mouse neuroblastoma cells (N1E-115) were studied using the suction pipette, voltage clamp technique. Pyrethroids increased the amplitude of the sodium current, sometimes by more than 200%. Activation of the sodium current occurred at more hyperpolarized potentials than under control conditions. The declining phase of the sodium current during depolarization was markedly slowed down and after repolarization of the membrane a large, slowly decaying sodium tail current developed. Pyrethroids did not affect the sodium current reversal potential, steady-state sodium inactivation or recovery from sodium channel inactivation. The amplitude of the pyrethroid-induced slow tail current was always proportional to the sodium current at the end of the preceding depolarizing pulse. The rate of decay of the slow tail current strongly depended on pyrethroid structure and increased in the order deltamethrin, cyphenothrin, fenfluthrin and phenothrin. The rate of decay further depended on membrane potential and temperature. Below -85 m V the instantaneous current-voltage relationship of the slow tail current showed a negative slope conductance. The tail current decayed more slowly at low temperatures. Arrhenius plots indicated that the relaxation of open sodium channels to a closed state involved a higher energy barrier for pyrethroid-affected than for normal channels. The energy barrier was higher after deltamethrin than after the non-cyano pyrethroid fenfluthrin. It is concluded that in mammalian neuronal membrane pyrethroids selectively reduce the rate of closing of sodium channels both during depolarization and after repolarization of the nerve membrane.
采用吸液管电压钳技术，研究了4种不同拟除虫菊酯类杀虫剂对内部灌注的培养小鼠神经母细胞瘤细胞（N1E-115）钠通道门控的影响。拟除虫菊酯类杀虫剂增加了钠电流的幅度，有时增幅超过200%。钠电流的激活发生在比对照条件下更超极化的电位。去极化期间钠电流的下降阶段明显减慢，膜复极化后出现一个大的、缓慢衰减的钠尾电流。拟除虫菊酯类杀虫剂不影响钠电流反转电位、稳态钠失活或从钠通道失活中的恢复。拟除虫菊酯诱导的缓慢尾电流的幅度始终与前一个去极化脉冲结束时的钠电流成正比。缓慢尾电流的衰减速率强烈依赖于拟除虫菊酯的结构，其衰减速率按溴氰菊酯、苯醚菊酯、苄呋菊酯和氯菊酯的顺序增加。衰减速率还取决于膜电位和温度。在-85mV以下，缓慢尾电流的瞬时电流-电压关系呈现负斜率电导。尾电流在低温下衰减更慢。阿累尼乌斯图表明，开放钠通道向关闭状态的松弛过程中，受拟除虫菊酯影响的通道比正常通道涉及更高的能垒。溴氰菊酯处理后的能垒高于非氰基拟除虫菊酯苄呋菊酯处理后的能垒。得出的结论是，在哺乳动物神经元膜中，拟除虫菊酯类杀虫剂在神经膜去极化期间和复极化后均选择性地降低钠通道的关闭速率。
