Fipronil modulation of GABAA receptor single-channel currents
Fipronil modulation of GABAA receptor single-channel currents
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DOI：
10.1002/ps.830
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发表时间：
2004-05-01
影响因子：
4.1
通讯作者：
Narahashi, T
中科院分区：
文献类型：
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作者：
Ikeda, T;Nagata, K;Narahashi, T
氟虫腈是第一种用于害虫防治的苯基吡唑类杀虫剂。虽然氟虫腈已知可以抑制GABA受体，但具体的作用机制仍有待观察。为了阐明锐劲特与哺乳动物GABA(A)系统相互作用的机制，用大鼠背根神经节神经元进行了单通道膜片钳实验。10um氟虫腈和10um GABA共同作用对主导状态电流(27pS)的幅度无明显影响。开放时间分布的直方图拟合成三个指数函数之和。喷施氟虫腈后，最快组分的比例略有增加，最慢组分的比例略有下降。因此，氟虫腈的平均开放时间从11.4ms减少到7.8ms。闭合时间分布的直方图拟合成四个指数函数之和。锐劲特10微米延长最慢时间常数，平均关闭时间由29.7ms延长至52.8ms。因此，减少了通道打开的频率。因此，锐劲特抑制GABA诱导的全细胞电流的部分原因是通道开放时间和通道开放频率的减少。(C)2004年化学工业学会
Fipronil is the first phenylpyrazole insecticide introduced for pest control. Although fipronil is known to inhibit GABA receptors, the detailed mechanism of action remains to be seen. In order to elucidate the mechanism of fipronil interaction with the mammalian GABA(A) system, single-channel patch clamp experiments were performed using rat dorsal root ganglion neurons. The amplitude of main conductance state (27 pS) current was not significantly altered by co-application of 10 muM fipronil and 10 muM GABA. The histograms of open time distribution were fitted to a sum of three exponential functions. After application of 10 muM fipronil, the proportion of the fastest component increased slightly and that of the slowest component decreased slightly. Thus, the mean open time was decreased from 11.4 ms to 7.8 ms by fipronil. The histograms of closed time distribution were fitted to a sum of four exponential functions. Fipronil 10 muM prolonged the slowest time constant resulting in a prolongation of the mean closed time from 29.7 ms to 52.8 ms. Thus, the frequency of channel openings was reduced. Thus, the fipronil suppression of GABA-induced whole-cell currents is caused in part by decreases in the channel open time and the frequency of channel openings. (C) 2004 Society of Chemical Industry