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Under physiological conditions, mitochondria localized near the apical membrane form a buffering zone that restricts the spread of Ca 2+ signals from the subplasmalemmal region to the cell interior, thereby protecting PACs from Ca 2+ -induced injury ( 2+ microdomains arising at close contact between the PM and mitochondria enable rapid mitochondrial Ca 2+ uptake, activation of TCA cycle enzymes, and stimulation of ATP production, a critical energy source for enzyme secretion and maintenance of electrolyte gradients ( 2+ indicators average signals over relatively large cytosolic volumes, whereas genetically encoded Ca 2+ sensors targeted to defined subcellular compartments are only beginning to be applied systematically in pancreatic models

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