Role of calcium in metabolic signaling between cardiac sarcoplasmic reticulum and mitochondria in vitro.
The role of Ca(2+) as a cytosolic signaling molecule between porcine cardiac sarcoplasmic reticulum (SR) ATPase and mitochondrial ATP production was evaluated in vitro. The Ca(2+) sensitivity of these processes was determined individually and in a reconstituted system with SR and mitochondria in a 0.5:1 protein-to-cytochrome aa(3) ratio. The half-maximal concentration (K(1/2)) of SR ATPase was 335 nM Ca(2+). The ATP synthesis dependence was similar with a K(1/2) of 243 nM for dehydrogenases and 114 nM for overall ATP production. In the reconstituted system, Ca(2+) increased thapsigargin-sensitive ATP production (maximum approximately 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 Ca(2+) concentrations (0 to approximately 500 nM). These data are consistent with a balanced activation of SR ATPase and mitochondrial ATP synthesis by Ca(2+) that contributes to a homeostasis of energy metabolism metabolites. It is suggested that this balanced activation by cytosolic Ca(2+) is partially responsible for the minimal alteration in energy metabolism intermediates that occurs with changes in cardiac workload in vivo.
Balaban
Robert S
RS
Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1061, USA. groverak@mcmaster.ca
Bose
Salil
S
French
Stephanie A
SA
Territo
Paul R
PR
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000187:drug effects / Q000378:metabolism; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D009243:NAD / Q000187:drug effects / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013347:Subcellular Fractions; D034421:Sus scrofa
D004791:Enzyme Inhibitors; D009243:NAD; D000255:Adenosine Triphosphate; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium