Store-operated Ca²⁺ entry-dependent Ca²⁺ refilling in the endoplasmic reticulum in astrocytes

Astrocytes regulate various brain functions, for which Ca²⁺ release from the endoplasmic reticulum (ER) often play crucial roles. Because astrocytic ER Ca²⁺ release is robust and frequent, the ER Ca²⁺ refilling mechanism should be critical for ongoing Ca²⁺ signaling in astrocytes. In this study, we focused on the putative functional significance of store-operated Ca²⁺ entry (SOCE) in ER Ca²⁺ refilling. We expressed the ER luminal Ca²⁺ indicator G-CEPIA1er in astrocytes in acute cortical slices to directly monitor the decrease and recovery of ER Ca²⁺ concentration upon spontaneous or norepinephrine-induced Ca²⁺ release. Inhibition of SOCE significantly slowed the recovery of ER Ca²⁺ concentration after Ca²⁺ release in astrocytes. This delayed recovery resulted in a prolonged decrease in the ER Ca²⁺ content in astrocytes with periodic spontaneous Ca²⁺ release, followed by the attenuation of cytosolic Ca²⁺ responses upon Ca²⁺ release. Therefore, our results provide direct evidence for the physiological significance of SOCE in ER Ca²⁺ refilling after ER Ca²⁺ release.