Astroglial Ca2+signaling is generated by the coordination of IP3R and store-operated Ca2+channels.
Astrocytes play key roles in the central nervous system and regulate local blood flow and synaptic transmission via intracellular calcium (Ca2+) signaling. Astrocytic Ca2+signals are generated by multiple pathways: Ca2+release from the endoplasmic reticulum (ER) via the inositol 1, 4, 5-trisphosphate receptor (IP3R) and Ca2+influx through various Ca2+channels on the plasma membrane. However, the Ca2+channels involved in astrocytic Ca2+homeostasis or signaling have not been fully characterized. Here, we demonstrate that spontaneous astrocytic Ca2+transients in cultured hippocampal astrocytes were induced by cooperation between the Ca2+release from the ER and the Ca2+influx through store-operated calcium channels (SOCCs) on the plasma membrane. Ca2+imaging with plasma membrane targeted GCaMP6f revealed that spontaneous astroglial Ca2+transients were impaired by pharmacological blockade of not only Ca2+release through IP3Rs, but also Ca2+influx through SOCCs. Loss of SOCC activity resulted in the depletion of ER Ca2+, 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 Ca2+-ATPase, contribute to the maintenance of astrocytic Ca2+store levels, ultimately enabling astrocytic Ca2+signaling.
Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa, Nagoya, Aichi, 464-8602, Japan.
Shigeo
S
Sakuragi
Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Fumihiro
F
Niwa
Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa, Nagoya, Aichi, 464-8602, Japan.
Yoichi
Y
Oda
Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Electronic address: mikosiba@brain.riken.jp.
Katsuhiko
K
Mikoshiba
Division of Biological Science, Graduate School of Science, Nagoya University, Furo-cho, Chikusa, Nagoya, Aichi, 464-8602, Japan; Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Nagoya Research Center for Brain & Neural Circuits, Nagoya University, Furo-cho, Chikusa, Nagoya, Aichi, 464-8602, Japan; Japan Science and Technology Agency, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan. Electronic address: hbannai@brain.riken.jp.
Hiroko
H
Bannai
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D006624:Hippocampus; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D002118:Calcium
Astrocyte; Ca(2+) signal; Endoplasmic reticulum; IP(3) receptor; SOC channel