Cytosolic and Endoplasmic Reticulum Ca²⁺ Concentrations Determine the Extent and the Morphological Type of Apoptosis, Respectively

During apoptosis, an increase in cytosolic Ca²⁺ concentration ([Ca²⁺]_c) accompanies the depletion of endoplasmic reticulum (ER). The actual roles of each of the two events in apoptosis are difficult to understand. In this work, we have modulated the basal [Ca ²⁺]_c and the thapsigargin (THG)-dependent reticular flux (i.e., by chelating extracellular Ca²⁺ or by modulating intracellular Ca²⁺ by 3-aminobenzamide [3-ABA]). We have found that these treatments alter these Ca²⁺ parameters in a differential way and, accordingly, affect apoptosis differentially. We have found that the increase in [Ca²⁺]_c is related to the extent of apoptosis, whereas the ER depletion affects the apoptotic nuclear morphology by shifting it towards the cleavage mode.