Micromolar and submicromolar Ca 2+ spikes regulating distinct cellular functions in pancreatic acinar cells

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