Astroglial Ca signaling is generated by the coordination of IPR and store-operated Ca channels.

Astrocytes play key roles in the central nervous system and regulate local blood flow and synaptic transmission via intracellular calcium (Ca) signaling. Astrocytic Ca signals are generated by multiple pathways: Ca release from the endoplasmic reticulum (ER) via the inositol 1, 4, 5-trisphosphate receptor (IPR) and Ca influx through various Ca channels on the plasma membrane. However, the Ca channels involved in astrocytic Ca homeostasis or signaling have not been fully characterized. Here, we demonstrate that spontaneous astrocytic Ca transients in cultured hippocampal astrocytes were induced by cooperation between the Ca release from the ER and the Ca influx through store-operated calcium channels (SOCCs) on the plasma membrane. Ca imaging with plasma membrane targeted GCaMP6f revealed that spontaneous astroglial Ca transients were impaired by pharmacological blockade of not only Ca release through IPRs, but also Ca influx through SOCCs. Loss of SOCC activity resulted in the depletion of ER Ca, suggesting that SOCCs are activated without store depletion in hippocampal astrocytes. Our findings indicate that sustained SOCC activity, together with that of the sarco-endoplasmic reticulum Ca-ATPase, contribute to the maintenance of astrocytic Ca store levels, ultimately enabling astrocytic Ca signaling.