Comparison of Ca 2 + , Sr 2 + , and Mn 2 + Fluxes in Mitochondria of the Perfused Rat Heart

The amount of readily exchangeable Ca in mitochondria of an isolated working rat heart is less than 10 ng-ions/g heart. We therefore conclude that either no Ca enters mitochondria or that the Ca which does enter is removed continuously. Using Sr* and Mn, we obtained evidence that the mitochondrial Na-Ca exchanger was indeed operational in releasing metal from mitochondria of the heart. When Ca in the perfusate was replaced by Sr*, we found that a significant amount of Sr* (approximately 100 ng-ions/g heart) entered mitochondria. When the heart then was returned to a Ca-containing perfusate, over 80% of the Sr* was washed out of mitochondria within 30 seconds. When low levels of Mn were added to the perfusate, we found that Mn accumulated in mitochondria irreversibly. This is evidence for the operation of the Na-Ca exchanger because Na was found to release Ca and Sr* but not Mn from isolated rat heart mitochondria. Our estimates indicate that when the Na-Ca exchanger is maximally operative, as in the Sr^-perfused heart, the flux of Sr* through mitochondria is at most 10% of the total flux needed for the activation of contraction. The low level of Ca in the mitochondria of Ca-perfused hearts suggests a much smaller flux of Ca through the mitochondria in this case. We therefore conclude that mitochondria play little if any role in the beat-to-beat regulation of normal Ca fluxes in the rat heart. Circ Res 47: 721-727, 1980