Comparison of Ca2+, Sr2+, and Mn2+ fluxes in mitochondria of the perfused rat heart.

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Abstract
The amount of readily exchangeable Ca2+ in mitochondria of an isolated working rat heart is < 10 ng-ions/g heart. Either no Ca2+ enters mitochondria or the Ca2+ which does enter is removed continuously. Using Sr2+ and Mn2+, evidence was obtained that the mitochondrial Na+-Ca2+ exchanger was operational in releasing metal from mitochondria of the heart. When Ca2+ in the perfusate was replaced by Sr2+, a significant amount of Sr2+ (.apprx. 100 ng-ions/g heart) entered mitochondria. The heart was returned to a Ca2+-containing perfusate. Over 80% of the Sr2+ was washed out of mitochondria within 30 s. When low levels of Mn2+ were added to the perfusate, Mn2+ irreversibly accumulated in mitochondria. This is evidence for the operation of the Na+-Ca2+ exchanger. Na+ released Ca2+ and Sr2+ but not Mn2+ from isolated rat heart mitochondria. When the Na+-Ca2+ exchanger is maximally operative, as in the Sr2+-perfused heart, the flux of Sr2+ through mitochondria apparently is at most 10% of the total flux needed for the activation of contraction. The low level of Ca2+ in the mitochondria of Ca2+-perfused hearts suggests a much smaller flux of Ca2+ through the mitochondria. Mitochondria play little if any role in the beat-to-beat regulation of normal Ca2+ fluxes in the rat heart.

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