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

Abstract

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.