A model showing the IP₃-induced Ca²⁺ mobilization from secretory granules and the secretory processes of astrocytes.

The tetrameric IP3R/Ca2+ channels are shown in red and blue columns while chromogranins A and B are shown in open and hatched circles, respectively. Only can chromogranin B, which interacts with CGA to form a CGA-CGB heterodimer at the pH of ER, couple to the tetrameric IP3Rs in the ER [75] whereas both chromogranins A and B, which form a CGA2CGB2 heterotetrameric complex at the acidic intragranular pH [94], couple to the tetrameric IP3Rs in secretory granules [75], [77], [78]. Stimuli at the cell surface (1) will lead to the production of IP3 at the plasma membrane, which will serve as the first signal to induce the IP3-dependent Ca2+ release from intracellular Ca2+ stores in the cytoplasm. Yet each intracellular Ca2+ store will respond differently to IP3 depending on the amount of IP3 produced and the sensitivity of the IP3R/Ca2+ channels to IP3. In light of the significantly higher sensitivity of the IP3R/Ca2+ channels of secretory granules than those of the ER [40], secretory granules will release Ca2+ (2), ahead of the ER (3), in response to low IP3 concentrations. This Ca2+ could play essential roles in initiating secretion by synaptic-like vesicles (4) and secretory granules (5), leading to secretion of the gliotransmitters (6).