LOCAL AND GLOBAL CYTOSOLIC CA2+ OSCILLATIONS IN EXOCRINE CELLS EVOKEDBY AGONISTS AND INOSITOL TRISPHOSPHATE

Submaximal stimulation with agonists generating inositol 1,4,5-trispho sphate (IP3) evokes cytosolic Ca2+ oscillations in many different cell types. In general, each Ca2+ rise is initiated from a specific region near the plasma membrane and then spreads as a wave throughout the ce ll. We now demonstrate that low (physiological) agonist concentrations evoke local cytosolic Ca2+ spikes in the secretory pole of single mou se pancreatic acinar cells that are particularly sensitive to blockade by the IP3 receptor antagonist heparin. These spikes can occur alone or repetitively or can precede longer lasting Ca2+ signals that spread throughout the cell. Intracellular IP3 application mimics these agoni st actions. The short-lasting local Ca2+ spikes provide an economical signaling mechanism and are of physiological significance since they a ctivate Ca2+-dependent Cl- and cation currents important for control o f fluid secretion.