Abstract
Cell death occurs under physiological and pathophysiological conditions in response to a number of signals and stresses. Our recent studies have revealed that a number of mechanisms of cell death induction are based on physiological processes. Apoptotic cells exhibit whole-cell shrinkage, termed apoptotic volume decrease (AVD). Activation of volume-sensitive outwardly rectifying anion channel (VSOR) is coupled to the AVD induced by a mitochondrion- or death receptor-mediated apoptosis inducer. The regulatory volume increase (RVI) is impaired in apoptotic cells. The AVD event precedes cytochrome c release, caspase activation and DNA laddering. Even without stimulation by any specific apoptotic inducer, apoptotic cell death is induced under the conditions where persistent cell shrinkage is compelled by physical or physiological maneuvers. Prevention of AVD rescues cell death caused by an apoptotic inducer or ischemia-reperfusion. On the other hand, excitotoxicity, lactacidosis or acidotoxicity causes persistent cell swelling, termed necrotic volume increase (NVI), and necrotic cell death in neuronal, glial and epithelial cells. Impairment of the regulatory volume decrease (RVD) due to disordered VSOR activities is associated with NVI. Acidotoxicity leads to activation of a novel type of anion channel which serves as an anion influx pathway. Prevention of NVI or restoration of RVD rescues necrotic cell death. Thus, it is concluded that dysfunction of cell volume regulation and disordered activities of anion channels play indispensable roles in apoptotic, necrotic and ischemic cell death. [J Physiol Sci. 2007;57 Suppl:S2]
