Ion Channels, Cell Volume, Cell Proliferation and Apoptotic Cell Death

At some stage cell proliferation requires an increase in cell volume and a typical hallmark of apoptotic cell death is cell shrinkage. The respective alterations of cell volume are accomplished by altered regulation of ion transport including ion channels. Thus, cell proliferation and apoptosis are both paralleled by altered activity of ion channels, which play an active part in these fundamental cellular mechanisms. Activation of anion channels allows exit of Cl?, osmolyte and HCO3 ? leading to cell shrinkage and acidification of the cytosol. K⁺ exit through K⁺ channels leads to cell shrinkage and a decrease in intracellular K⁺ concentration. K⁺ channel activity is further important for maintenance of the cell membrane potential – a critical determinant of Ca²⁺ entry through Ca²⁺ channels. Cytosolic Ca²⁺ may both activate mechanisms required for cell proliferation and stimulate enzymes executing apoptosis. The effect of enhanced cytosolic Ca²⁺ activity depends on the magnitude and temporal organisation of Ca²⁺ entry. Moreover, a given ion channel may support both cell proliferation and apoptosis, and specific ion channel blockers may abrogate both fundamental cellular mechanisms, depending on cell type, regulatory environment and condition of the cell. Clearly, further experimental effort is needed to clarify the role of ion channels in the regulation of cell proliferation and apoptosis.