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Am J Physiol Cell Physiol 284: C285-C293, 2003; doi:10.1152/ajpcell.00129.2002
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Vol. 284, Issue 2, C285-C293, February 2003

Role of calcium in metabolic signaling between cardiac sarcoplasmic reticulum and mitochondria in vitro

Robert S. Balaban, Salil Bose, Stephanie A. French, and Paul R. Territo

Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1061

The role of Ca2+ as a cytosolic signaling molecule between porcine cardiac sarcoplasmic reticulum (SR) ATPase and mitochondrial ATP production was evaluated in vitro. The Ca2+ sensitivity of these processes was determined individually and in a reconstituted system with SR and mitochondria in a 0.5:1 protein-to-cytochrome aa3 ratio. The half-maximal concentration (K1/2) of SR ATPase was 335 nM Ca2+. The ATP synthesis dependence was similar with a K1/2 of 243 nM for dehydrogenases and 114 nM for overall ATP production. In the reconstituted system, Ca2+ increased thapsigargin-sensitive ATP production (maximum ~5-fold) with minimal changes in mitochondrial reduced nicotinamide adenine dinucleotide (NADH). NADH concentration remained stable despite graded increases in NADH turnover induced over a wide range of Ca2+ concentrations (0 to ~500 nM). These data are consistent with a balanced activation of SR ATPase and mitochondrial ATP synthesis by Ca2+ that contributes to a homeostasis of energy metabolism metabolites. It is suggested that this balanced activation by cytosolic Ca2+ is partially responsible for the minimal alteration in energy metabolism intermediates that occurs with changes in cardiac workload in vivo.

adenosine 5'-triphosphate; energy metabolism; calciumadenosinetriphosphatase; reduced nicotinamide adenine dinucleotide; porcine heart


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