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

• Published in: Circulation research 1980-11, Vol.47 (5), p.721-727
• Main Authors: Hunter, D R, Komai, H, Haworth, R A, Jackson, M D, Berkoff, H A
• Format: Article
• Language: English
• Subjects: Animals; Calcium - physiology; Egtazic Acid - pharmacology; Manganese - physiology; Mitochondria, Heart - physiology; Rats; Strontium - physiology; Time Factors
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.47.5.721

The amount of readily exchangeable Ca2+ in mitochondria of an isolated working rat heart is less than 10 ng-ions/g heart. We therefore conclude that either no Ca2+ enters mitochondria or that the Ca+ which does enter is removed continuously. Using Sr2+ and Mn2+, we obtained evidence that the mitochondrial Na+-Ca2+ exchanger was indeed operational in releasing metal from mitochondria of the heart. When Ca2+ in the perfusate was replaced by Sr2+, we found that a significant amount of Sr2+ (approximately 100 ng-ions/g heart) entered mitochondria. When the heart then was returned to a Ca2+-containing perfusate, over 80% of the Sr2+ was washed out of mitochondria within 30 seconds. When low levels of Mn2+ were added to the perfusate, we found that Mn2+ accumulated in mitochondria irreversibly. This is evidence for the operation of the Na+-Ca2+ exchanger because Na+ was found to release Ca2+ and Sr2+ but not Mn2+ from isolated rat heart mitochondria. Our estimates indicate that when the Na+-Ca2+ exchanger is maximally operative, as in the Sr2+-perfused heart, the flux of Sr2+ through mitochondria 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 in this case. We therefore conclude that mitochondria play little if any role in the beat-to-beat regulation of normal Ca2+ fluxes in the rat heart.