Micromolar and submicromolar Ca2+ spikes regulating distinct cellular functions in pancreatic acinar cells

Agonists induce Ca2+ spikes, waves and oscillations initiating at a trigger zone in exocrine acinar cells via Ca2+ release from intracellular Ca2+ stores, Using a low affinity ratiometric Ca2+ indicator dye, benzothiazole coumarin (ETC), we found that high concentrations of agonists transiently increased Ca2+ concentrations to the micromolar range (>10 mu M) in the trigger zone, Comparison with results obtained with a high affinity Ca2+ indicator dye, fura-2, indicated that. fura-2 was in fact saturated with Ca2+ during the agonist-induced Ca2+ spikes in the trigger zone, We further revealed that the micromolar Ca2+ spikes were necessary for inducing exocytosis of zymogen granules investigated using capacitance measurements, In contrast, submicromolar Ca2+ spikes selectively gave rise to sequential activation of luminal and basal ion channels, These results suggest new functional diversity in Ca2+ spikes and a critical role for the micromolar Ca2+ spikes in exocytotic secretion from exocrine acinar cells, Our data also emphasize the value of investigating the Ca2+ signalling using low affinity Ca2+ indicators.