The loss of cell volume is a fundamental and universal characteristic of pr
ogrammed cell death. However, what was once thought to be a passive, second
ary feature of the cell death process has now become an area of research in
terest. Recent studies have integrated cell volume regulation and the movem
ent of ions with the activation of apoptosis. A dramatic reduction of potas
sium and sodium concentration has been shown to occur in apoptotic cells th
at exhibit a shrunken morphology. Furthermore, maintaining the normal physi
ological intracellular concentration of monovalent ions, particularly potas
sium, inhibits the activation and activity of the death cascades. Thus, the
role ions play during apoptosis is more extensive than just facilitation o
f the loss of cell volume. In this article, we will review the concepts of
cell Volume regulation and the loss of volume during apoptosis. Additionall
y, we will underscore our current understanding of ion movement as it relat
es to the activation of the cell death process. BIOCHEM PHARMACOL 56;12:154
9-1559, 1998. (C) 1998 Elsevier Science Inc.