The effect of ionophore A23187 and 2,4-dinitrophenol on the structure and function of cultured liver cells

Abstract

Adult rat hepatocytes maintained in primary culture have been used as a model system to study cellular injury dependent upon extracellular calcium. Incubation of hepatocytes with ionophore A23187 (1 to 5 μ m) resulted in leakage of cytoplasmic enzymes, an increase in the number of cells stained with trypan blue, blebing of the plasma membrane, and changes in mitochondrial structure characterized by mitochondrial swelling. Moreover, a 60% decrease in cellular ATP was observed to precede changes in cellular permeability. These cytotoxic alterations induced by ionophore were dependent upon the presence of extracellular calcium. In contrast, 2,4-dinitrophenol depleted ATP much more extensively and induced extensive swelling of mitochondria at concentrations which failed to induce significant leakage of cytoplasmic enzymes. Cytotoxic changes induced by ionophore were potentiated by 2,4-dinitrophenol but not ethionine which has been shown to cause a reduction in cellular ATP levels. However, ethionine potentiated the cytotoxicity induced by 2,4-dinitrophenol.