Studies on the mode of action of insecticides : Novel methods for chemical screening.

神经元型烟碱乙酰胆碱受体通道（AChR）在中枢神经系统中起着复杂的作用。Ca ~（2+）离子通过突触前膜上的烟碱型AChR进入神经元，对包括NMDA和GABA（A）受体在内的多种离子通道进行调节。为了阐明杀虫剂对神经元烟碱型AChR的作用机制，采用全细胞膜片钳和单通道膜片钳技术研究了吡虫啉、杀螟丹、新斯的明和西维因对神经元烟碱型AChR的影响。结果表明，这四种杀虫剂通过不同的作用机制调节烟碱AChR。吡虫啉作为一种部分激动剂，主要产生亚电导状态电流，而杀螟丹作为一种开放通道阻断剂在烟碱乙酰胆碱受体。新斯的明和西维因直接阻断烟碱AChR，类似于杀螟丹。烯啶虫胺，（E）-N-（6-氯-3-吡啶甲基）-N-乙基-N '-甲基-2-硝基-亚乙烯基二胺，是一种作用于 ...更多信息 烟碱乙酰胆碱受体通道（AChR）。我们研究了烯啶虫胺对大鼠克隆性嗜铬细胞瘤PC 12细胞中烟碱型AChR的神经元类型的影响，使用膜片钳技术，以澄清在单通道水平的作用机制。烯啶虫胺本身诱导的单通道电流介导的神经元烟碱AChR。ACh和烯啶虫胺的共同应用打开通道，表现出两种电导状态。烯啶虫胺的存在降低了主电导水平的比例，增加了亚电导水平。ACh和烯啶虫胺共同作用的主电导态电流的开放时间和闭合时间分布与Ach诱导的电流相似，但爆发持续时间的分布与Ach诱导的电流不同。单通道动力学的这些变化的结果在解释的影响，烯啶虫胺对神经元烟碱AChR的主要电导状态电流的开口的概率降低。烯啶虫胺对乙酰胆碱诱发电流的影响被认为是其毒性作用的直接原因。少

The neuronal nicotinic acetylcholine receptor-channels (AChR) play a vital role in the central nervous system in a complicated manner. Several ion channels including NMDA and GABA(A) receptors are modulated by Ca2+ ions which enter through the neuronal nicotinic AChRs in the presynaptic membranes. In order to clarify the detailed mechanism of action of insecticides on the neuronal nicotinic AChR, effects of imidacloprid, cartap, neostigmine and carbaryl were studied using the whole-cell and single-channel patch clamp techniques. Results indicate that these four insecticides modulate nicotinic AChR by different mechanisms of action. Imidacloprid acts as a partial agonist generating predominantly subconductance state currents, whereas cartap acts as an open channel blocker at the nicotinic AChR. Neostigmine and carbaryl directly block the nicotinic AChR similar to cartap. Nitenpyram, (E)-N-(6-chloro-3-pyridylmethyl)-N-ethyl-N '-methyl-2-nitro-vinylidenediamine, is known to act on the nic … More otinic acetylcholine receptor-channel (AChR). We examined the effects of nitenpyram on the neuronal type of the nicotinic AChR in rat clonal phaeochromocytoma PC 12 cells using a patch clamp technique to clarify the mechanisms of action at the single-channel level. Nitenpyram itself induced single-channel currents mediated by the neuronal nicotinic AChR. Co-application of ACh and nitenpyram opened the channels exhibiting the two conductance states. The proportion of main conductance levels was decreased and that of subconductance levels was increased in the presence of nitenpyram. The open time and closed time distribution, but not for the burst duration, for the main conductance state currents with co-application of ACh and nitenpyram were similar to those of Ach-induced current. These changes of single-channel kinetics result in a decrease in probability of openings of main conductance state currents explaining the effects of nitenpyram on the neuronal nicotinic AChR. The effects of nitenpyram on the acetylcholine-induced current are deemed directly responsible for the toxic actions in animals. Less