title: Mitochondrial oxidative phosphorylation in hearts subjected to Ca2+ depletion and Ca2+ repletion.
abstract: Repletion of Ca2+ in the Ca2+-depleted heart has been shown to produce cardiac dysfunction, myocardial cell damage, intracellular Ca2+ overload, and defects in sarcolemmal and sarcoplasmic reticulum function (Ca2+ paradox). Although these alterations in the Ca2+-paradox heart are associated with a depression in the high-energy phosphate stores, little information regarding changes in mitochondrial oxidative phosphorylation is available. Perfusion of rat hearts with Ca2+-free medium for 5 min followed by reperfusion with a medium containing 1.25 mmol/L Ca2+ for 10 min depressed mitochondrial state 3 respiration, respiratory control index, ADP/O ratio, and rate of oxidative phosphorylation without any change in state 4 respiration. These alterations were partially prevented when the reperfusion was carried out with a medium containing low Ca2+ (0.10-0.50 mmol/L). Treatment of heart with inhibitors of sarcolemmal Ca2+ channels (verapamil and diltiazem) or inhibitors of Na+/Ca2+ exchange (KB-R7943) and Na+/H+ exchange (amiloride) failed to modify changes in mitochondrial function due to Ca2+ paradox. Likewise, antioxidants N-acetylcysteine and N-(2-mercaptopropionyl)-glycine and an oxyradical-scavenging mixture of superoxide dismutase and catalase were ineffective in preventing the mitochondrial alterations in the Ca2+-paradox heart. Incubation of mitochondria with various concentrations of Ca2+ inhibited oxidative phosphorylation; this Ca2+-induced change in mitochondrial function was not affected by different oxyradical-scavenging systems. These observations suggest that defects in mitochondrial function in the Ca2+-paradox heart may be due to the occurrence of intracellular Ca2+ overload rather than the development of oxidative stress.
authors.affiliation: Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, MB R2H 2A6, Canada.
authors.forename: Zhanna
authors.initials: Z
authors.lastname: Makazan
authors.forename: Harjot K
authors.initials: HK
authors.lastname: Saini-Chohan
authors.forename: Naranjan S
authors.initials: NS
authors.lastname: Dhalla
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004396:Coloring Agents; D006334:Heart Function Tests; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D008929:Mitochondria, Heart / Q000502:physiology*; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012430:Ruthenium Red; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002121:Calcium Channel Blockers; D004396:Coloring Agents; D012430:Ruthenium Red; D008353:Mannitol; D013482:Superoxide Dismutase; D017301:Ca(2+) Mg(2+)-ATPase; D002118:Calcium