A necessary role for cell shrinkage in apoptosis.

The loss of cell volume is a fundamental and universal characteristic of programmed cell death. However, what was once thought to be a passive, secondary feature of the cell death process has now become an area of research interest. Recent studies have integrated cell volume regulation and the movement of ions with the activation of apoptosis. A dramatic reduction of potassium and sodium concentration has been shown to occur in apoptotic cells that exhibit a shrunken morphology. Furthermore, maintaining the normal physiological intracellular concentration of monovalent ions, particularly potassium, inhibits the activation and activity of the death cascades. Thus, the role ions play during apoptosis is more extensive than just facilitation of the loss of cell volume. In this article, we will review the concepts of cell volume regulation and the loss of volume during apoptosis. Additionally, we will underscore our current understanding of ion movement as it relates to the activation of the cell death process.