Effect of calcium chelation on the ion content of liver mitochondria in carbon tetrachloride-poisoned rats.

When toxic doses of CC& were given to rats, there ensued marked accumulations of Ca++ and inorganic orthophosphate by whole liver commencing 6 hours after treatment. When these livers were homogenized in 0.25 M sucrose, the Ca++ and Pi concentrations of the mitochondria subsequently harvested were elevated several fold, reflecting the higher levels of these ions in the whole tissue. The Kf concentration usually declined in the whole tissue and decreased in the mitochondria. In these mitochondria, respiratory rate and respiratory control were markedly depressed. If, on the other hand, the liver samples were homogenized in 0.25 M sucrose containing the Ca++ chelator, ethylenediaminetetraacetate (or EGTA or DCTA), the mitochondria often contained much lower amounts of Ca+f and Pi, and the respiratory rate and respiratory control were closer to normal levels. Whether a chelator was used or not, the changes in Ca++ and K+ concentration in the whole tissue or mitochondria did not appear to be closely related to each other. The effect of the chelators on ionic composition appeared to result from the prevention of accumulation of Ca* and Pi by the mitochondria subsequent to the homogenization of the tissue. It is concluded that the major portion of the changes in content of Ca++ of isolated liver mitochondria following CC14 poisoning which have been reported by others occurred during the isolation of these organelles and must be considered to be artifacts of the isolation procedure. The residual chelator-resistant changes in respiratory function and ionic composition may reflect actual qualitative changes in the mitochondria extant in these organelles in vivo.