Sequential-replenishment mechanism of exocytosis in pancreatic acini

Here we report exocytosis of zymogen granules, as examined by multiphoton e xcitation imaging in intact pancreatic acini, Cholecystokinin induces Ca2oscillations that trigger exocytosis when the cytosolic Ca2+ concentration exceeds 1 muM. Zymogen granules fused with the plasma membrane maintain the ir Omega -shaped profile for an average of 220 s and serve as targets for s equential fusion of granules that are located within deeper layers of the c ell. This secondary exocytosis occurrs as rapidly as the primary exocytosis and accounts for most exocytotic events. Granule-granule fusion does not s eem to precede primary exocytosis, indicating that secondary fusion events may require a plasma-membrane factor, This sequential-replenishment mechani sm of exocytosis allows the cell to take advantage of a large supply of fus ion-ready granules without needing to transport them to the plasma membrane .