Role of mitochondria in Ca(2+) oscillations and shape of Ca(2+) signals in pancreatic acinar cells

• Published in: Biochemical pharmacology Vol. 63; no. 2; pp. 283 - 292
• Main Authors: Camello-Almaraz, C, Salido, G M, Pariente, J A, Camello, P J
• Format: Journal Article
• Language: English
• Published: England 15.01.2002
• Subjects: Animals; Calcium - metabolism; Calcium Signaling - physiology; Cytosol - metabolism; In Vitro Techniques; Mice; Mitochondria - physiology; Pancreas - cytology; Pancreas - metabolism
• ISSN: 0006-2952
• DOI: 10.1016/S0006-2952(01)00830-9

We studied the role of mitochondria in Ca(2+) signals in fura-2 loaded exocrine pancreatic acinar cells. Mitochondrial depolarization in response to carbonylcyanide-p-tryfluoromethoxyphenyl hydrazone or rotenone (assessed by confocal microscopy using rhodamine-123) induced a partial but statistically significant reduction in the decay of Ca(2+) signals under different experimental conditions. Spreading of Ca(2+) waves evoked by the pancreatic secretagogue cholecystokinin cholecystokinin octapeptide was accelerated by mitochondrial inhibitors, whereas the cytosolic Ca(2+) concentration ([Ca(2+)](i)) oscillations in response to physiological levels of this hormone were suppressed by rotenone and carbonylcyanide-p-tryfluoromethoxyphenyl hydrazone. Oligomycin, an inhibitor of mitochondrial ATP synthase, did no affect either propagation of calcium waves nor [Ca(2+)](i) oscillations. Individual mitochondria of rhod-2 loaded acinar cells showed heterogeneous matrix Ca(2+) concentration increases in response to oscillatory and maximal levels of cholecystokinin octapeptide. On the other hand, using Ba(2+) for unequivocal study of capacitative calcium entry we found that mitochondrial inhibitors did not affect this process. Our results show that although the role of mitochondria as a Ca(2+) clearing system in exocrine cells is quantitatively secondary, they play an essential role in the spatial propagation of Ca(2+) waves and in the development of [Ca(2+)](i) oscillations.