Balance of unidirectional monovalent ion fluxes in cells undergoing apoptosis: why does Na+/K+ pump suppression not cause cell swelling?

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Abstract
Non‐technical summary  Apoptosis is a crucial mechanism for tissue maintenance and deregulation of apoptosis may lead to catastrophic consequences in humans (e.g. cancer). The present work is a first attempt to quantitatively characterize rearrangement of the monovalent ion fluxes in cells during apoptosis. An established model of apoptosis induced by staurosporine in lymphoid U937 cells is used to experimentally measure cellular Cl− content and fluxes, K+, Na+ and water content as well as ouabain‐sensitive and ‐resistant Rb+ fluxes. A mathematical model is developed to account for the unidirectional ion fluxes and water balance in a cell as a whole. A decrease in the channel permeability of the plasma membrane for Na+ proved to be crucial for preventing cell swelling due to the decrease in Na+/K+ pump activity in cells undergoing apoptosis whereas opening of the K+ and Cl− channels is not required. Supplemental Table S1 is given for easy calculating flux balance under specified conditions.

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