EVIDENCE FOR 2 CALCIUM-DEPENDENT STEPS AND A SODIUM-DEPENDENT STEP IN THE MECHANISM OF CELL KILLING BY CALCIUM-IONS IN THE PRESENCE OF IONOPHORE A23187

  • 1 January 1985
    • journal article
    • research article
    • Vol. 120  (2) , 304-315
Abstract
Elevated intracellular Ca2+ appears to play an important role in the mechanism of cell killing in certain pathologic states such as ischemia. Aspects of the biochemical mechanism of cell killing were examined by elevated intracellular Ca2+ using as a model system cultured fibroblasts treated with ionophore A23187 [calcimycin] in Ca2+ containing medium. Evidence was obtained for 2 Ca2+-mediated steps and a Na+-mediated step in the cell killing process. The first Ca2+-mediated step occurs in low extracellular Ca2+ concentrations (1-100 .mu.M) and exhibits a variety of characteristics in common with the arachidonic acid release response stimulated under the same conditions. These results are consistent with the arachidonic acid release response constituting or closely monitoring the initial injury process. The second Ca2+ mediated process is achieved at near physiologic extracellular Ca2+ concentrations in the absence of A23187. Killing of cells injured by the 2 Ca2+-dependent steps requires extracellular Na+ ions at half or more the physiologic concentration.