星形胶质细胞内质网中钙库操纵性钙内流依赖的钙再填充。
Store-operated Ca entry-dependent Ca refilling in the endoplasmic reticulum in astrocytes.
机构信息
Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 133-0033, Japan.
Division of Cellular and Molecular Pharmacology, Nihon University School of Medicine, 30-1 Oyaguchi Kamicho, Itabashi-ku, Tokyo, 173-8610, Japan.
出版信息
Biochem Biophys Res Commun. 2020 Feb 19;522(4):1003-1008. doi: 10.1016/j.bbrc.2019.12.006. Epub 2019 Dec 5.
Astrocytes regulate various brain functions, for which Ca release from the endoplasmic reticulum (ER) often play crucial roles. Because astrocytic ER Ca release is robust and frequent, the ER Ca refilling mechanism should be critical for ongoing Ca signaling in astrocytes. In this study, we focused on the putative functional significance of store-operated Ca entry (SOCE) in ER Ca refilling. We expressed the ER luminal Ca indicator G-CEPIA1er in astrocytes in acute cortical slices to directly monitor the decrease and recovery of ER Ca concentration upon spontaneous or norepinephrine-induced Ca release. Inhibition of SOCE significantly slowed the recovery of ER Ca concentration after Ca release in astrocytes. This delayed recovery resulted in a prolonged decrease in the ER Ca content in astrocytes with periodic spontaneous Ca release, followed by the attenuation of cytosolic Ca responses upon Ca release. Therefore, our results provide direct evidence for the physiological significance of SOCE in ER Ca refilling after ER Ca release.
星形胶质细胞调节各种大脑功能，其中内质网 (ER) 中的 Ca 释放通常起着至关重要的作用。由于星形胶质细胞 ER Ca 释放是强大而频繁的，因此 ER Ca 再填充机制对于星形胶质细胞中的持续 Ca 信号传导应该是至关重要的。在这项研究中，我们专注于储存操作的 Ca 进入 (SOCE) 在 ER Ca 再填充中的潜在功能意义。我们在急性皮质切片中的星形胶质细胞中表达了内质网腔 Ca 指示剂 G-CEPIA1er，以直接监测自发或去甲肾上腺素诱导的 Ca 释放后 ER Ca 浓度的下降和恢复。SOCE 的抑制显著减缓了 Ca 释放后 ER Ca 浓度的恢复。这种延迟的恢复导致周期性自发 Ca 释放的星形胶质细胞中 ER Ca 含量的持续下降，随后 Ca 释放时细胞浆 Ca 反应的减弱。因此，我们的结果为 SOCE 在 ER Ca 释放后 ER Ca 再填充中的生理意义提供了直接证据。
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