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 (BTC), we found that high concentrations of agonists transiently increased Ca2+ concentrations to the micromolar range (>10 microM) 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.
Ito
K
K
Department of Physiology, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Japan.
Miyashita
Y
Y
Kasai
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D052160:Benzothiazoles; D002118:Calcium / Q000378:metabolism*; D003374:Coumarins; D005089:Exocytosis; D005456:Fluorescent Dyes; D016257:Fura-2; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008856:Microscopy, Fluorescence; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism; D010782:Photolysis; D013844:Thiazoles
D052160:Benzothiazoles; D003374:Coumarins; D005456:Fluorescent Dyes; D013844:Thiazoles; C104515:benzothiazole coumarin; D000109:Acetylcholine; D002118:Calcium; D016257:Fura-2