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使用对称有机阳离子溶液研究 P2X7 离子渗透。

Using Symmetrical Organic Cation Solutions to Study P2X7 Ion Permeation.

机构信息

Centre National de la Recherche Scientifique, University of Strasbourg, CAMB UMR 7199, Strasbourg, France.

Channel-Receptors Unit, Institut Pasteur, UMR 3571, Paris, France.

出版信息

Methods Mol Biol. 2022;2510:239-252. doi: 10.1007/978-1-0716-2384-8_12.

DOI:10.1007/978-1-0716-2384-8_12
PMID:35776328
Abstract

P2X7 receptors are ATP-gated ion channels permeable to metal cations, such as Na, K, and Ca. They also exhibit permeability to various large molecular weight species, reaching up to 900 Da, in a process known as macropore formation, which is a unique functional hallmark across the P2X family. While well-documented in a range of different cell types, the molecular mechanism underlying this phenomenon is poorly understood, and has been clouded through the use of electrophysiological methodology prone to artifacts as a result of significant changes in ionic concentrations in asymmetric conditions. In this chapter, we discuss the permeation properties of P2X7, the related methodological challenges and the use of symmetrical organic cation solutions as a useful technique for probing P2X7 permeation.

摘要

P2X7 受体是一种 ATP 门控离子通道,对金属阳离子(如 Na、K 和 Ca)具有通透性。它们还表现出对各种大分子物质的通透性,最大可达 900 Da,这一过程称为大孔形成,是 P2X 家族的独特功能标志。尽管在多种不同的细胞类型中都有很好的记录,但这种现象背后的分子机制还不太清楚,并且由于不对称条件下离子浓度的显著变化,容易产生电生理学方法的假象,这使得该机制更加复杂。在本章中,我们将讨论 P2X7 的渗透性、相关的方法学挑战以及使用对称有机阳离子溶液作为探测 P2X7 渗透性的有用技术。

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本文引用的文献

1
Full-Length P2X Structures Reveal How Palmitoylation Prevents Channel Desensitization.全长 P2X 结构揭示了棕榈酰化如何防止通道脱敏。
Cell. 2019 Oct 17;179(3):659-670.e13. doi: 10.1016/j.cell.2019.09.017. Epub 2019 Oct 3.
2
A fast and reproducible cell- and 96-well plate-based method for the evaluation of P2X7 receptor activation using YO-PRO-1 fluorescent dye.一种基于细胞和96孔板的快速且可重复的方法,用于使用YO-PRO-1荧光染料评估P2X7受体激活情况。
J Biol Methods. 2017 Jan 20;4(1):e64. doi: 10.14440/jbm.2017.136. eCollection 2017.
3
A Mechanism-Based Approach to P2X7 Receptor Action.
基于机制的 P2X7 受体作用方法。
Mol Pharmacol. 2019 Apr;95(4):442-450. doi: 10.1124/mol.118.115022. Epub 2019 Feb 8.
4
ATP-Gated P2X7 Receptors Require Chloride Channels To Promote Inflammation in Human Macrophages.三磷酸腺苷门控 P2X7 受体需要氯离子通道促进人巨噬细胞炎症反应。
J Immunol. 2019 Feb 1;202(3):883-898. doi: 10.4049/jimmunol.1801101. Epub 2018 Dec 31.
5
A central role for P2X7 receptors in human microglia.P2X7 受体在人类小胶质细胞中起核心作用。
J Neuroinflammation. 2018 Nov 21;15(1):325. doi: 10.1186/s12974-018-1353-8.
6
New Insights Into Permeation of Large Cations Through ATP-Gated P2X Receptors.关于大阳离子通过ATP门控P2X受体渗透的新见解。
Front Mol Neurosci. 2018 Jul 31;11:265. doi: 10.3389/fnmol.2018.00265. eCollection 2018.
7
Non-nucleotide Agonists Triggering P2X7 Receptor Activation and Pore Formation.触发P2X7受体激活和孔形成的非核苷酸激动剂。
Front Pharmacol. 2018 Feb 1;9:39. doi: 10.3389/fphar.2018.00039. eCollection 2018.
8
The Elusive P2X7 Macropore. elusive P2X7 巨孔
Trends Cell Biol. 2018 May;28(5):392-404. doi: 10.1016/j.tcb.2018.01.005. Epub 2018 Feb 10.
9
The P2X7 receptor forms a dye-permeable pore independent of its intracellular domain but dependent on membrane lipid composition.P2X7 受体形成一种染料渗透性孔道,该孔道不依赖其细胞内结构域,但依赖于膜脂组成。
Elife. 2017 Sep 18;6:e31186. doi: 10.7554/eLife.31186.
10
P2X7 receptor large pore signaling in avian Müller glial cells.禽类穆勒胶质细胞中P2X7受体的大孔信号传导
J Bioenerg Biomembr. 2017 Jun;49(3):215-229. doi: 10.1007/s10863-017-9717-9. Epub 2017 Jun 1.