Effects of calcium channel blocking agents on membrane microviscosity and calcium in the liver of the carbon tetrachloride treated rat.

Membrane microviscosity was determined from the polarized fluorescence of diphenylhexatriene in plasma membranes and microsomes prepared from the liver of carbon tetrachloride treated rats. It was greatly depressed between 12 and 24 hr after the administration of the carbon tetrachloride. Depression of microviscosity was also seen in the liposomes which were prepared from these membranes. There were decreases in phospholipid content and phospholipid methyltransferase activity, but these changes did not appear to explain the decreased microviscosity. A large accumulation of calcium occurred in the liver cells between 12 and 24 hr after the administration of carbon tetrachloride. Chlorpromazine, verapamil and nifedipine, when administered prior to the carbon tetrachloride, partially reduced the later accumulation of calcium and reduced the degree of histological damage observed. When these agents were administered 12 hr after the administration of carbon tetrachloride, they did not reduce the subsequent accumulation of calcium. When administered prior to and 7 hr after carbon tetrachloride, they had a small but potentially significant effect on the microviscosity change. It is suggested that at low levels of microviscosity a critical threshold may exist below which entry of calcium into the cell is poorly controlled and that calcium channel blocking agents may be ineffective if administered at a time when membrane microviscosity is very low. Tissue calcium accumulation was associated with visible cell damage.