Type 2 inositol 1,4,5-trisphosphate receptor is predominantly involved in agonist-induced Ca²⁺ signaling in Bergmann glia

Ca²⁺ release via inositol 1,4,5-trisphosphate (IP₃) receptors (IP₃Rs) plays a crucial role in astrocyte functions such as modulation of neuronal activity and regulation of local blood flow in the cerebral cortex and hippocampus. Bergmann glia are unipolar cerebellar astrocytes that release Ca²⁺ through IP₃Rs in response to the activation of G_q-coupled receptors. The composition of the three subtypes of IP₃R is a factor that determines the spatiotemporal pattern of Ca²⁺ release. However, the functional expression of IP₃R subtypes and their contribution to Ca²⁺ release in Bergmann glia remain controversial. In this study, we first characterized the Ca²⁺ response in Bergmann glia to noradrenaline and histamine stimulation in organotypic cultures of the mouse cerebellum using a Ca²⁺ indicator, Inverse-Pericam, and found that Bergmann glial processes exhibit a higher agonist-induced Ca²⁺ indicator response than the soma. Furthermore, we performed Ca²⁺ imaging using mutant mice lacking each IP₃R subtype. This revealed that Bergmann glia lacking type 2 IP₃R exhibited reduced responses to noradrenaline or histamine compared with wild-type Bergmann glia and Bergmann glia with other genotypes, suggesting that type 2 IP₃R is the major functional IP₃R subtype involved in agonist-induced Ca²⁺ release in Bergmann glia, although types 1 and 3 IP₃R could also contribute to rapid agonist-induced [Ca²⁺]_i elevation in the processes.