Necrotic volume increase and the early physiology of necrosis

Whether a lethally injured mammalian cell undergoes necrosis or apoptosis m ay be determined by the early activation of specific ion channels at the ce ll surface. Apoptosis requires K+ and Cl- efflux, which leads to cell shrin king, an active phenomenon termed apoptotic volume decrease (AVD). In contr ast, necrosis has been shown to require Na+ influx through membrane carrier s and more recently through stress-activated non-selective cation channels (NSCCs). These ubiquitous channels are kept dormant in viable cells but bec ome activated upon exposure to free-radicals. The ensuing Na+ influx leads to cell swelling, an active response that may be termed necrotic volume inc rease (NVI). This review focuses on how AVID and NVI become conflicting for ces at the beginning of cell injury, on the events that determine irreversi bility and in particular, on the ion fluxes that decide whether a cell is t o die by necrosis or by apoptosis. (C) 2001 Elsevier Science Inc. All right s reserved.