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.