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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. ORCID:, Petersen, Ole H. ORCID:, 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: 17 Oct 2022 10:35

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