Effect of halomethanes on intracellular calcium distribution in hepatocytes.

Exposure of isolated rat hepatocytes to hepatotoxic halomethanes results in a 40-60% decrease in intracellular Ca2+ content. The order of halomethane potency (CBrCl3 CCl4 CHCl3) suggests that this effect requires halomethane metabolism by the hepatic mixed function oxidase system. Although the Ca2+ sequestering ability of the endoplasmic reticulum is destroyed by CBrCl3 and CCl4, it appears that much of the Ca2+ lost from the cell is mitochondrial in origin. Paradoxically, saturating concentrations of CCl4 cause a marked increase in cell Ca2+. CCl4 also causes an acute increase in cytoplasmic free Ca2+ (from about 60 nM to about 90 nM), but this effect does not appear to require CCl4 metabolism and is probably a result of direct action of CCl4 on the plasma membrane.