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ATP depletion inhibits Ca2+ release, influx and extrusion in pancreatic acinar cells but not pathological Ca2+ responses induced by bile

Barrow, Stephanie L, Voronina, Svetlana G., Xavier, Gabriela da Silva, Chvanov, Misha A., Longbottom, Rebecca E., Gerasimenko, Oleg V., Petersen, Ole H., Rutter, Guy A. and Tepikin, Alexei V. 2008. ATP depletion inhibits Ca2+ release, influx and extrusion in pancreatic acinar cells but not pathological Ca2+ responses induced by bile. Pflügers Archiv - European Journal of Physiology 455 (6) , pp. 1025-1039. 10.1007/s00424-007-0360-x

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Here, we describe novel mechanisms limiting a toxic cytosolic Ca2+ rise during adenosine 5′-triphosphate (ATP) depletion. We studied the effect of ATP depletion on Ca2+ signalling in mouse pancreatic acinar cells. Measurements of ATP in isolated cells after adenovirus-mediated expression of firefly luciferase revealed that the cytosolic ATP concentration fell from approximately 1 mM to near zero after treatment with oligomycin plus iodoacetate. ATP depletion resulted in the inhibition of Ca2+ extrusion, which was accompanied by a remarkably synchronous inhibition of store-operated Ca2+ influx. Alternative inhibition of Ca2+ extrusion by carboxyeosin had a much smaller effect on Ca2+ influx. The coordinated metabolic inhibition of Ca2+ influx and extrusion suggests the existence of a common ATP-dependent master regulator of both processes. ATP-depletion also suppressed acetylcholine (ACh)-induced Ca2+ oscillations, which was due to the inhibition of Ca2+ release from internal stores. This could be particularly important for limiting Ca2+ toxicity during periods of hypoxia. In contrast, metabolic control of Ca2+ influx and Ca2+ release from internal stores spectacularly failed to prevent large toxic Ca2+ responses induced by bile acids—activators of acute pancreatitis (a frequent and often fatal disease of the exocrine pancreas). The bile acids taurolithocholic acid 3-sulphate (TLC-S), taurochenodeoxycholic acid (TCDC) and taurocholic acid (TC) were used in our experiments. Neither Ca2+ release from internal stores nor Ca2+ influx triggered by bile acids were inhibited by ATP depletion, emphasising the danger of these pathological mechanisms.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Calcium signalling; Calcium influx; Pancreas; ATP; Calcium release
Publisher: Springer Verlag
ISSN: 0031-6768
Last Modified: 10 Mar 2020 13:46

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