Functional expression of Drosophila para sodium channels. Modulation by the membrane protein TipE and toxin pharmacology.
Functional expression of Drosophila para sodium channels. Modulation by the membrane protein TipE and toxin pharmacology.
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DOI：
10.1085/jgp.110.2.119
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发表时间：
1997-08
影响因子：
3.8
通讯作者：
Cohen, C J
中科院分区：
文献类型：
--
作者：
Warmke, J W;Reenan, R A;Wang, P;Qian, S;Arena, J P;Wang, J;Wunderler, D;Liu, K;Kaczorowski, G J;Van der Ploeg, L H;Ganetzky, B;Cohen, C J
果蝇帕拉钠通道α亚基在非洲爪蟾卵母细胞中单独表达，并与假定的果蝇钠通道辅助亚基tipE组合表达。tipE与帕拉的共表达导致钠电流水平升高和电流衰减加速。帕拉/TipE钠通道具有与天然通道相似的生物物理学和药理学特性。然而，这些通道的药理学不同于脊椎动物钠通道的药理学：（a）来自沟状风毛藻的毒素II，其减缓失活，以类似的亲和力结合到帕拉和一些哺乳动物钠通道（Kd <10 nM），但该毒素导致帕拉/TipE失活速率比哺乳动物通道的失活速率降低100倍;（B）帕拉钠通道对河豚毒素阻断的敏感性大于10倍;和（c）拟除虫菊酯类杀虫剂氯菊酯的修饰对帕拉钠通道的效力大于对大鼠脑IIA型钠通道的效力的100倍。我们的研究结果表明，拟除虫菊酯杀虫剂的选择性毒性至少部分是由于拟除虫菊酯对昆虫钠通道的亲和力大于对哺乳动物钠通道的亲和力。
The Drosophila para sodium channel α subunit was expressed in Xenopus oocytes alone and in combination with tipE, a putative Drosophila sodium channel accessory subunit. Coexpression of tipE with para results in elevated levels of sodium currents and accelerated current decay. Para/TipE sodium channels have biophysical and pharmacological properties similar to those of native channels. However, the pharmacology of these channels differs from that of vertebrate sodium channels: (a) toxin II from Anemonia sulcata, which slows inactivation, binds to Para and some mammalian sodium channels with similar affinity (K d ≅ 10 nM), but this toxin causes a 100-fold greater decrease in the rate of inactivation of Para/TipE than of mammalian channels; (b) Para sodium channels are >10-fold more sensitive to block by tetrodotoxin; and (c) modification by the pyrethroid insecticide permethrin is >100-fold more potent for Para than for rat brain type IIA sodium channels. Our results suggest that the selective toxicity of pyrethroid insecticides is due at least in part to the greater affinity of pyrethroids for insect sodium channels than for mammalian sodium channels.