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

Ca(2+) release via inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)Rs) 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 Ca(2+) through IP(3)Rs in response to the activation of G(q)-coupled receptors. The composition of the three subtypes of IP(3)R is a factor that determines the spatiotemporal pattern of Ca(2+) release. However, the functional expression of IP(3)R subtypes and their contribution to Ca(2+) release in Bergmann glia remain controversial. In this study, we first characterized the Ca(2+) response in Bergmann glia to noradrenaline and histamine stimulation in organotypic cultures of the mouse cerebellum using a Ca(2+) indicator, Inverse-Pericam, and found that Bergmann glial processes exhibit a higher agonist-induced Ca(2+) indicator response than the soma. Furthermore, we performed Ca(2+) imaging using mutant mice lacking each IP(3)R subtype. This revealed that Bergmann glia lacking type 2 IP(3)R exhibited reduced responses to noradrenaline or histamine compared with wild-type Bergmann glia and Bergmann glia with other genotypes, suggesting that type 2 IP(3)R is the major functional IP(3)R subtype involved in agonist-induced Ca(2+) release in Bergmann glia, although types 1 and 3 IP(3)R could also contribute to rapid agonist-induced [Ca(2+)](i) elevation in the processes.