The influence of lanthanum on the subcellular distribution of calcium in the perfused dog heart.

A newly developed method was used to make a direct study of the influence of lanthanum on the subcellular distribution of isotopic and elemental calcium in the isolated perfused dog heart. The trivalent cation was introduced into the heart for the last 5 min of a 60 min perfusion period. Developed pressure and dP/dt were monitored continually from a fluid filled balloon positioned within the left ventricular chamber. At the end of the perfusion period, calcium was fixed within the myocardium by rapid freezing followed by vacuum desiccation at -60 degrees C. Enriched populations of sarcolemma and mitochondria were then obtained utilizing a newly developed nonpolar density gradient ultracentrifugation technique. Lanthanum was found to decrease dP/dt by 82.5% without significant changes in contractile rate. Atomic absorption spectrophotometric analysis revealed that lanthanum was associated with a 48.8% decrease in sarcolemmal calcium and a 159.6% increase in mitochondrial calcium. Lanthanum caused a 40.2% increase in the mitochondrial tissue/medium 45Ca ratio without significantly altering the isotropic activity of the sarcolemma. The results confirm that lanthanum-induced negative inotropy is associated with a displacement of sarcolemma-associated calcium. Surprisingly, the diminished contractility occurs with an increase in mitochondrial-associated calcium.