Structure-activity relationships for the action of 11 pyrethroid insecticides on rat Nav1.8 sodium channels expressed in Xenopus oocytes
Structure-activity relationships for the action of 11 pyrethroid insecticides on rat Nav1.8 sodium channels expressed in Xenopus oocytes
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DOI：
10.1016/j.taap.2005.06.022
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发表时间：
2006-03-15
影响因子：
3.8
通讯作者：
Soderlund, DM
中科院分区：
文献类型：
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作者：
Choi, JS;Soderlund, DM
拟除虫菊酯类杀虫剂与电压敏感性钠通道结合，改变其门控动力学，从而破坏神经功能。本文介绍了11种结构不同的商业拟除虫菊酯杀虫剂对大鼠Na（v）1.8钠通道亚型，河豚毒素抗性，拟除虫菊酯敏感的感觉神经元的钠电流，在非洲爪蟾卵母细胞中表达的主要载体的行动。所有11种化合物产生特征性钠尾电流后，去极化脉冲，范围从快速衰减的单指数电流（丙烯菊酯，顺式菊酯和二氯菊酯）持久的双指数电流（氟氯氰菊酯，氯氟氰菊酯，氯氰菊酯和溴氰菊酯）。其余化合物（联苯菊酯、甲氰菊酯、氰戊菊酯和七氟菊酯）的尾电流为单指数，衰减动力学介于这些极端之间。重建的电流进行单独的拟除虫菊酯修饰的亚群的通道揭示了两种类型的拟除虫菊酯修饰的电流。第一种类型，发现与顺式菊酯，丙烯菊酯，二氯苯菊酯和七氟菊酯，激活相对迅速，并在40毫秒的去极化部分失活。第二种类型，发现与氯氰菊酯，氟氯氰菊酯，氯氰菊酯，溴氰菊酯，甲氰菊酯和氰戊菊酯，激活更慢，并没有deletably在40毫秒的去极化。只有联苯菊酯没有产生明显适合这些类别的修改电流。在所有情况下，修饰通道的速率与复极化后尾电流衰减的速率密切相关。通过重复刺激，氟氯氰菊酯、氯氰菊酯、氯氰菊酯和溴氰菊酯对Na（v）1.8钠通道的修饰增强了2.3至3.4倍;这种效应似乎是由于持续开放通道的积累而不是优先结合到开放通道状态。甲氰菊酯是最有效的化合物对Na（v）1.8钠通道的角度，无论是休息或使用依赖性修饰。当考虑使用依赖性时，氯氰菊酯、溴氰菊酯和七氟菊酯接近甲氰菊酯的有效性。伤害性神经元中Na（v）1.8钠通道的选择性表达表明，这些通道可能是拟除虫菊酯在皮肤暴露后产生感觉异常的重要靶点。(c)2005年爱思唯尔公司All rights reserved.
Pyrethroid insecticides bind to voltage-sensitive sodium channels and modify their gating kinetics, thereby disrupting nerve function. This paper describes the action of 11 structurally diverse commercial pyrethroid insecticides on the rat Na(v)1.8 sodium channel isoform, the principal carrier of the tetrodotoxin-resistant, pyrethroid-sensitive sodium current of sensory neurons, expressed in Xenopus laevis oocytes. All 11 compounds produced characteristic sodium tail currents following a depolarizing pulse that ranged from rapidly-decaying monoexponential currents (allethrin, cismethrin and perniethrin) to persistent biexponential currents (cyfluthrin, cyhalothrin, cypermethrin and deltamethrin). Tail currents for the remaining compounds (bifenthtin, fenpropathrin, fenvalerate and tefluthrin) were monoexponential and decayed with kinetics intermediate between these extremes. Reconstruction of currents carried solely by the pyrethroid-modified subpopulation of channels revealed two types of pyrethroid-modified currents. The first type, found with cismethrin, allethrin, permethrin and tefluthrin, activated relatively rapidly and inactivated partially during a 40-ms depolarization. The second type, found with cypermethrin, cyfluthrin, cyllalothrin, deltamethrin, fenpropathrin and fenvalerate, activated more slowly and did not delectably inactivate during a 40-ms depolarization. Only bifenthrin did not produce modified currents that fit clearly into either of these categories. In all cases, the rate of of modified channels was strongly correlated with the rate of tail Current decay following repolarization. Modification of Na(v)1.8 sodium channels by cyfluthrin, cyllalothrin, cypermethrin and deltamethrin was enhanced 2.3- to 3.4-fold by repetitive stimulation; this effect appeared to result from the accumulation of persistently open channels rather than preferential binding to open channel states. Fenpropathrin was the most effective compound against Na(v)1.8 sodium channels from the perspective of either resting or use-dependent modification. When use dependence is taken into account, cypermethrin, deltamethrin and tefluthrin approached the effectiveness of fenpropathrin. The selective expression of Na(v)1.8 sodium channels in nociceptive neurons suggests that these channels may be important targets for pyrethroids in the production of paresthesia following dermal exposure. (c) 2005 Elsevier Inc. All rights reserved.