| First Author | Okubo Y | Year | 2019 |
| Journal | Glia | Volume | 67 |
| Issue | 1 | Pages | 113-124 |
| PubMed ID | 30306640 | Mgi Jnum | J:269379 |
| Mgi Id | MGI:6273102 | Doi | 10.1002/glia.23531 |
| Citation | Okubo Y, et al. (2019) Inositol 1,4,5-trisphosphate receptor type 2-independent Ca(2+) release from the endoplasmic reticulum in astrocytes. Glia 67(1):113-124 |
| abstractText | Accumulating evidence indicates that astrocytes are actively involved in the physiological and pathophysiological functions of the brain. Intracellular Ca(2+) signaling, especially Ca(2+) release from the endoplasmic reticulum (ER), is considered to be crucial for the regulation of astrocytic functions. Mice with genetic deletion of inositol 1,4,5-trisphosphate receptor type 2 (IP3 R2) are reportedly devoid of astrocytic Ca(2+) signaling, and thus widely used to explore the roles of Ca(2+) signaling in astrocytic functions. While functional deficits in IP3 R2-knockout (KO) mice have been found in some reports, no functional deficit was observed in others. Thus, there remains a controversy regarding the functional significance of astrocytic Ca(2+) signaling. To address this controversy, we re-evaluated the assumption that Ca(2+) release from the ER is abolished in IP3 R2-KO astrocytes using a highly sensitive imaging technique. We expressed the ER luminal Ca(2+) indicator G-CEPIA1er in cortical and hippocampal astrocytes to directly visualize spontaneous and stimulus-induced Ca(2+) release from the ER. We found attenuated but significant Ca(2+) release in response to application of norepinephrine to IP3 R2-KO astrocytes. This IP3 R2-independent Ca(2+) release induced only minimal cytosolic Ca(2+) transients but induced robust Ca(2+) increases in mitochondria that are frequently in close contact with the ER. These results indicate that ER Ca(2+) release is retained and is sufficient to increase the Ca(2+) concentration in close proximity to the ER in IP3 R2-KO astrocytes. |
