Role of stress in the initial injury stages of cell killing by altered intracellular calcium

A variety of cultured cell types are effectively killed by Ca^{2 +}-carrying ionophores (A23187, ionomycin and lasalocid) in the presence of adequate extracellular concentrations of Ca^{2 +} and Na ⁺, although cell killing mechanisms independent of these ions also exist. Previous studies identified 2 injury stages (termed stage I and stage II injury) at which the A23187-induced killing process in 3T3 fibroblasts is interrupted in the presence of low extracellular Ca^{2 +} concentrations and in the absence of extracellular Na ⁺, respectively. The present studies confirm the generality of stage II injury in Ca^{2 +} -mediated cell killing, but demonstrate a requirement for concomitant stress conditions (e.g., osmotic or oxidative stress) for expression of stage I injury.