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 (IP₃ R2). These IP₃ R2-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 IP₃ R2-KO astrocytes has been re-evaluated using intraorganellar Ca²⁺ imaging techniques. The new results indicated that IP₃ R2-independent Ca²⁺ release may generate Ca²⁺ nanodomains around the ER, which may help explain the absence of functional deficits in IP₃ R2-KO mice.