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可视化星形细胞内 Ca 动员。

Visualization of astrocytic intracellular Ca mobilization.

机构信息

Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, 133-0033, Japan.

Division of Cellular and Molecular Pharmacology, Nihon University School of Medicine, Tokyo, 173-8610, Japan.

出版信息

J Physiol. 2020 May;598(9):1671-1681. doi: 10.1113/JP277609. Epub 2019 Mar 18.

Abstract

Astrocytes generate robust intracellular Ca concentration changes (Ca signals), which are assumed to regulate astrocytic functions that play crucial roles in the regulation of brain functions. One frequently used strategy for exploring the role of astrocytic Ca signalling is the use of mice deficient in the type 2 inositol 1,4,5-trisphosphate receptor (IP R2). These IP R2-knockout (KO) mice are reportedly devoid of Ca mobilization from the endoplasmic reticulum (ER) in astrocytes. However, they have shown no functional deficits in several studies, causing a heated debate as to the functional relevance of ER-mediated Ca signalling in astrocytes. Recently, the assumption that Ca mobilization from the ER is absent in IP R2-KO astrocytes has been re-evaluated using intraorganellar Ca imaging techniques. The new results indicated that IP R2-independent Ca release may generate Ca nanodomains around the ER, which may help explain the absence of functional deficits in IP R2-KO mice.

摘要

星形胶质细胞会产生强烈的细胞内钙离子浓度变化(钙信号),这些变化被认为可以调节星形胶质细胞的功能,而这些功能在调节大脑功能方面起着至关重要的作用。一种常用于探索星形胶质细胞钙信号作用的策略是使用缺乏 2 型肌醇 1,4,5-三磷酸受体(IP R2)的小鼠。据报道,这些 IP R2 敲除(KO)小鼠的星形胶质细胞中没有内质网(ER)的钙离子动员。然而,在几项研究中,它们并没有表现出功能缺陷,这引发了一场关于 ER 介导的钙离子信号在星形胶质细胞中的功能相关性的激烈争论。最近,使用细胞器内钙离子成像技术重新评估了 IP R2-KO 星形胶质细胞中 ER 内钙离子动员缺失的假设。新的结果表明,IP R2 不依赖的钙离子释放可能会在 ER 周围产生钙离子纳米区,这可能有助于解释 IP R2-KO 小鼠缺乏功能缺陷的原因。

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