Role of mitochondria in Ca(2+) oscillations and shape of Ca(2+) signals in pancreatic acinar cells.
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.
Camello-Almaraz
C
C
Department of Physiology, Faculty of Veterinary Sciences, University of Extremadura, 10071, Caceres, Spain.
Salido
G M
GM
Pariente
J A
JA
Camello
P J
PJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008928:Mitochondria / Q000502:physiology*; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism
D002118:Calcium