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

神经元烟碱乙酰胆碱受体通道（AChR）在中枢神经系统中起着复杂的重要作用。包括NMDA和GABA(A)受体在内的几个离子通道受到Ca2+离子的调节，Ca2+离子通过突触前膜的神经元烟碱achr进入。为了阐明杀虫剂对神经元烟碱性AChR的作用机理，采用全细胞和单通道膜片钳技术研究了吡虫啉、卡泰泰、新斯的明和西威因对神经元烟碱性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性AChR。吡虫啉作为部分激动剂主要产生亚电导状态电流，而cartap在烟碱AChR中作为开放通道阻滞剂。新斯的明和西威因直接阻断烟碱性AChR，类似于卡塔普。Nitenpyram, (E)- n -（6-氯-3-吡啶甲基）- n -乙基-n '-甲基-2-硝基-偏乙基二胺，已知作用于乙酰胆碱受体通道（AChR）。我们利用膜片钳技术研究了尼坦吡仑对大鼠克隆性嗜铬细胞瘤pc12细胞中烟碱性AChR神经元类型的影响，以阐明其在单通道水平上的作用机制。Nitenpyram本身诱导由神经元尼古丁AChR介导的单通道电流。ACh和nitenpyram的共同应用打开了显示两种电导状态的通道。硝酸乙啶的存在降低了主电导水平的比例，增加了亚电导水平的比例。ACh和nitenpyram共同应用的主电导状态电流的开路时间和闭合时间分布与ACh感应电流相似，但在突发持续时间上不同。这些单通道动力学的变化导致主电导状态电流打开的概率降低，这解释了尼汀吡仑对神经元烟碱性AChR的影响。尼坦吡仑对乙酰胆碱诱导电流的影响被认为是动物中毒的直接原因。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