Excitation-contraction coupling in heart: VII. Calcium accumulation in subcellular particles in congestive heart failure

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Abstract

The ability of heavy microsomes and mitochondria, isolated from the control and failing hearts of genetically dystrophic hamsters (BIO 14.6 strain), to accumulate calcium was examined. The rate and extent of energy-linked calcium binding (in the absence of oxalate) by the heavy microsomes of the failing heart were markedly depressed. The calcium uptake (in the presence of 5 mM oxalate) by the heavy microsomes of the failing heart was similar to that of the control heart. On the other hand, both the rate and extent of energy-linked calcium binding (in the absence of Pi and succinate) and calcium uptake (in the presence of 4 mM Pi and 5 mM succinate) by mitochondria were greatly reduced in the failing heart in comparison to the control. No difference in the total adenosine triphosphatase activities (Ca++-Mg++ stimulated) of heavy microsomes or mitochondria was observed between the control and failing hearts. These results indicate an abnormality of subcellular membranes of the failing heart to bind calcium and support the growing conviction concerning the defective “calcium pump” as a molecular abnormality associated with a moderate degree of congestive heart failure.

Authors

Prakash V. Sulakhe, Naranjan S. Dhalla