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伊维菌素增强皮质神经元中ATP诱导的离子电流:P2X4受体功能表达的证据?

Ivermectin potentiates ATP-induced ion currents in cortical neurones: evidence for functional expression of P2X4 receptors?

作者信息

Lalo Ulyana, Verkhratsky Alexei, Pankratov Yuri

机构信息

Faculty of Medicine, Imperial College, London W12 0 NN, UK.

出版信息

Neurosci Lett. 2007 Jun 27;421(2):158-62. doi: 10.1016/j.neulet.2007.03.078. Epub 2007 May 31.

DOI:10.1016/j.neulet.2007.03.078
PMID:17566648
Abstract

We examined the effects of an antiparasitic agent ivermectin on ATP- and alpha,beta-methylene-ATP (alpha,beta-me-ATP)-activated currents in neurones acutely isolated from slices of somato-sensory cortex of 17-22 days old CBL57 mice. Membrane currents were monitored using whole-cell patch clamp combined with a "concentration-clamp" fast agonist application system. Ivermectin potentiated membrane currents induced by both ATP and alpha,beta-me-ATP applied alone or in the presence of broad P2X antagonist PPADS. Ivermectin also significantly increased amplitude and frequency of spontaneous P2X-mediated EPSCs recorded from cortical slices incubated with mixture of glutamate (CNQX, D-APV, SYM2081), GABA (picrotoxin), nicotinic cholinoreceptor (hexamethonium) antagonists and sodium channel blocker tetrodotoxin. These results indicate functional expression of P2X4 receptors in cortical neurones and their involvement in purinergic synaptic transmission in cortex.

摘要

我们研究了抗寄生虫药伊维菌素对从17 - 22日龄CBL57小鼠体感皮层切片急性分离的神经元中ATP和α,β-亚甲基-ATP(α,β-me-ATP)激活电流的影响。使用全细胞膜片钳结合“浓度钳”快速激动剂施加系统监测膜电流。伊维菌素增强了单独施加或在广泛的P2X拮抗剂PPADS存在下ATP和α,β-me-ATP诱导的膜电流。伊维菌素还显著增加了从用谷氨酸(CNQX、D-APV、SYM2081)、GABA(匹鲁卡品)、烟碱胆碱受体(六甲铵)拮抗剂和钠通道阻滞剂河豚毒素混合物孵育的皮层切片记录的自发性P2X介导的兴奋性突触后电流(EPSCs)的幅度和频率。这些结果表明P2X4受体在皮层神经元中的功能性表达及其参与皮层中的嘌呤能突触传递。

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