Visualization of astrocytic intracellular Ca2+ mobilization

Astrocytes generate robust intracellular Ca2+ concentration changes (Ca2+ signals), which are assumed to regulate astrocytic functions that play crucial roles in the regulation of brain functions. One frequently used strategy for exploring the role of astrocytic Ca2+ signalling is the use of mice deficient in the type 2 inositol 1,4,5‐trisphosphate receptor (IP3R2). These IP3R2‐knockout (KO) mice are reportedly devoid of Ca2+ mobilization from the endoplasmic reticulum (ER) in astrocytes. However, they have shown no functional deficits in several studies, causing a heated debate as to the functional relevance of ER‐mediated Ca2+ signalling in astrocytes. Recently, the assumption that Ca2+ mobilization from the ER is absent in IP3R2‐KO astrocytes has been re‐evaluated using intraorganellar Ca2+ imaging techniques. The new results indicated that IP3R2‐independent Ca2+ release may generate Ca2+ nanodomains around the ER, which may help explain the absence of functional deficits in IP3R2‐KO mice. Visualization of Ca2+ mobilization from the ER in IP3R2‐KO astrocytes using intraorganellar Ca2+ imaging techniques. Genetically encoded Ca2+ indicators for the ER (magenta) and mitochondria (cyan) but not for the cytosol (grey) successfully visualized Ca2+ release from the ER in IP3R2‐KO astrocytes.