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大鼠培养皮质星形胶质细胞 P2X7 受体的电生理学分类。

Electrophysiological classification of P2X7 receptors in rat cultured neocortical astroglia.

机构信息

Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Leipzig, Germany.

出版信息

Br J Pharmacol. 2010 Aug;160(8):1941-52. doi: 10.1111/j.1476-5381.2010.00736.x.

Abstract

BACKGROUND AND PURPOSE

P2X7 receptors are ATP-gated cation channels mediating important functions in microglial cells, such as the release of cytokines and phagocytosis. Electrophysiological evidence that these receptors also occur in CNS astroglia is rare and rather incomplete.

EXPERIMENTAL APPROACH

We used whole-cell patch-clamp recordings to search for P2X7 receptors in astroglial-neuronal co-cultures prepared from the cerebral cortex of rats.

KEY RESULTS

All the astroglial cells investigated responded to ATP with membrane currents, reversing around 0 mV. These currents could be also detected in isolated outside-out patch vesicles. The results of the experiments with the P2X [alpha,beta-methylene ATP and 2'-3'-O-(4-benzoyl) ATP] and P2Y receptor agonists [adenosine 5'-O-(2-thiodiphosphate), uridine 5'-diphosphate, uridine 5'-triphosphate (UTP) and UDP-glucose] suggested the involvement of P2X receptors in this response. The potentiation of ATP responses in a low divalent cation or alkaline bath, but not by ivermectin, made it likely that a P2X7 receptor is operational. Blockade of the ATP effect by the P2X7 antagonists Brilliant Blue G, calmidazolium and oxidized ATP corroborated this assumption.

CONCLUSIONS AND IMPLICATIONS

Rat cultured cortical astroglia possesses functional P2X7 receptors. It is suggested that astrocytic P2X7 receptors respond to high local ATP concentrations during neuronal injury.

摘要

背景与目的

P2X7 受体是一种 ATP 门控阳离子通道,在小胶质细胞中介导重要功能,如细胞因子的释放和吞噬作用。这些受体也存在于中枢神经系统星形胶质细胞中的电生理证据很少且相当不完整。

实验方法

我们使用全细胞膜片钳记录技术,在从大鼠大脑皮层制备的星形胶质细胞-神经元共培养物中寻找 P2X7 受体。

主要结果

所有研究的星形胶质细胞对 ATP 均有膜电流反应,反转电位约为 0 mV。这些电流也可以在分离的外面向外式膜片囊泡中检测到。用 P2X[alpha,beta-亚甲基 ATP 和 2'-3'-O-(4-苯甲酰基) ATP]和 P2Y 受体激动剂[腺苷 5'-O-(2-硫代二磷酸盐)、尿苷 5'-二磷酸、尿苷 5'-三磷酸 (UTP)和 UDP-葡萄糖]进行的实验结果表明,P2X 受体参与了这种反应。在低二价阳离子或碱性浴中增强 ATP 反应,但不被伊维菌素增强,这使得 P2X7 受体可能在起作用。P2X7 拮抗剂 Brilliant Blue G、氯米唑利和氧化型 ATP 阻断 ATP 效应进一步证实了这一假设。

结论和意义

大鼠培养的皮质星形胶质细胞具有功能性 P2X7 受体。据推测,星形胶质细胞 P2X7 受体在神经元损伤时对局部高浓度的 ATP 作出反应。

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本文引用的文献

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Guide to Receptors and Channels (GRAC), 4th Edition.《受体与通道指南》(第4版)
Br J Pharmacol. 2009 Nov;158 Suppl 1(Suppl 1):S1-254. doi: 10.1111/j.1476-5381.2009.00499.x.
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Signaling at purinergic P2X receptors.嘌呤能P2X受体信号传导。
Annu Rev Physiol. 2009;71:333-59. doi: 10.1146/annurev.physiol.70.113006.100630.
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ATP-gated P2X cation-channels.ATP门控的P2X阳离子通道
Neuropharmacology. 2009 Jan;56(1):208-15. doi: 10.1016/j.neuropharm.2008.06.067. Epub 2008 Jul 9.
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Evidence for functional P2X4/P2X7 heteromeric receptors.功能性P2X4/P2X7异聚体受体的证据。
Mol Pharmacol. 2007 Dec;72(6):1447-56. doi: 10.1124/mol.107.035980. Epub 2007 Sep 4.

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