title: Stimulatory effects of calcium on respiration and NAD(P)H synthesis in intact rat heart mitochondria utilizing physiological substrates cannot explain respiratory control in vivo.
abstract: Mitochondrial TCA cycle dehydrogenase enzymes have been shown to be stimulated by Ca(2+) under various substrate and ADP incubation conditions in an attempt to determine and understand the role of Ca(2+) in maintaining energy homeostasis in working hearts. In this study, we tested the hypothesis that, at physiological temperature and 1 mM extramitochondrial free magnesium, Ca(2+) can stimulate the overall mitochondrial NAD(P)H generation flux in rat heart mitochondria utilizing pyruvate and malate as substrates at both subsaturating and saturating concentrations. In both cases, we found that, in the physiological regime of mitochondrial oxygen consumption observed in the intact animal and in the physiological range of cytosolic Ca(2+) concentration averaged per beat, Ca(2+) had no observable stimulatory effect. A modest apparent stimulatory effect (22-27%) was observable at supraphysiological maximal ADP-stimulated respiration at 2.5 mM initial phosphate. The stimulatory effects observed over the physiological Ca(2+) range are not sufficient to make a significant contribution to the control of oxidative phosphorylation in the heart in vivo.
authors.affiliation: Biotechnology and Bioengineering Center and Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226.
authors.forename: Kalyan C
authors.initials: KC
authors.lastname: Vinnakota
authors.affiliation: Biotechnology and Bioengineering Center and Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226.
authors.forename: Ranjan K
authors.initials: RK
authors.lastname: Dash
authors.affiliation: Biotechnology and Bioengineering Center and Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226. Electronic address: dbeard@mcw.edu.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Beard
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry; D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D019069:Cell Respiration; D004305:Dose-Response Relationship, Drug; D007656:Ketoglutaric Acids / Q000737:chemistry; D008293:Malates / Q000737:chemistry; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000502:physiology; D009243:NAD / Q000737:chemistry; D009249:NADP / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000737:chemistry; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D014233:Tricarboxylic Acids / Q000737:chemistry
chemical_list: D007656:Ketoglutaric Acids; D008293:Malates; D014233:Tricarboxylic Acids; D009243:NAD; D009249:NADP; D000244:Adenosine Diphosphate; C030298:malic acid; D010100:Oxygen; D002118:Calcium