Differential mechanism of action of the pyrethroid tetramethrin on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels.
Differential mechanism of action of the pyrethroid tetramethrin on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels.
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发表时间：
1994-08
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通讯作者：
H. Tatebayashi;T. Narahashi
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作者：
H. Tatebayashi;T. Narahashi
大鼠背根神经节神经元具有河豚毒素敏感性（TTX-S）和河豚毒素抵抗性（TTX-R）钠通道。已知拟除虫菊酯杀虫剂可使钠通道长时间开放，但对两种类型的钠通道产生不同的影响。采用原代培养的大鼠背根神经节神经元进行全细胞膜片钳实验。在TTX-S钠通道中，胺菊酯使阶跃去极化过程中的慢钠电流有所增加，复极化时出现一个缓慢上升和下降相的尾钠电流。在去极化过程中，即使钠电流已经消退，尾电流也会发展。在TTX-R钠通道中，胺菊酯使阶跃去极化时的慢钠电流显著增加，复极化时产生大的瞬时尾电流并缓慢衰减。胺菊酯使TTX-S和TTX-R通道的稳态钠通道失活曲线向超极化方向移动。胺菊酯也使TTX-S和TTX-R通道的钠电导-电压曲线向超极化方向移动，且后者的影响比前者更强。在测试的最高浓度10 μ M的浓度下，胺菊酯仅修饰了12%的TTX-S钠通道，而TTX-R中的修饰高达81%。即使在10 nM时，也有1.3%的TTX-R钠通道被修饰;这是胺菊酯作为杀虫剂的高效力的原因。（250字处删节）
Rat dorsal root ganglion neurons are endowed with tetrodotoxin-sensitive(TTX-S) and tetrodotoxin-resistant (TTX-R) sodium channels. The pyrethroid insecticides, which are known to keep sodium channels open for a prolonged period of time, cause differential effects on the two types of sodium channels. The whole-cell patch clamp experiments were performed with rat dorsal root ganglion neurons in primary culture. In TTX-S sodium channels, the slow sodium current during step depolarization was increased somewhat by tetramethrin, and a tail sodium current with a slowly rising and falling phase appeared upon repolarization. The tail current developed even after the sodium current during depolarization had subsided. In TTX-R sodium channels, the slow sodium current during step depolarization was increased markedly by tetramethrin, and upon repolarization a large instantaneous tail current was generated and decayed slowly. The steady-state sodium channel inactivation curve was shifted by tetramethrin in the hyperpolarizing direction in both TTX-S and TTX-R channels. The sodium conductance-voltage curve also was shifted by tetramethrin in the hyperpolarizing direction in both TTX-S and TTX-R channels, and the latter was affected more strongly than the former. At a concentration of 10 microM, the highest concentration tested, tetramethrin modified only 12% of the TTX-S sodium channels, whereas the modification was as high as 81% in the TTX-R. Even at 10 nM, 1.3% of TTX-R sodium channels were modified; this accounts for the high potency of tetramethrin as an insecticide.(ABSTRACT TRUNCATED AT 250 WORDS)