Role of mitochondrial calcium transport in failing heart.
Mitochondrial calcium uptake, but not binding, like microsomal calcium uptake in failing human hearts, was less than the control values for dog, rabbit, and hamster hearts. Decrease in mitochondrial calcium binding and uptake was observed in genetically myopathic hamsters (BIO 14.6) at early, moderate, and late stages of congestive heart failure. Inhibitors of mitochondrial calcium transport, Dicumarol, dinitrophenol, and sodium azide, were found to produce a rapid fall in contractility of the isolated rat heart. Inability of rat hearts to generate contractile force on perfusion with Na+- or K+-free medium was associated with an increase in mitochondrial calcium uptake. A dramatic increase in mitochondrial calcium uptake was observed on perfusing rat hearts with control medium after CA++-free medium. No change in mitochondrial calcium uptake was noted in acute ischemic dog myocardium or hypoxic rat heart in which contractile force was severely depressed. Both mitochondrial calcium transport and contractility were decreased on perfusing rat hearts with substrate-free medium; however, the change in calcium uptake was secondary to the fall in contractile force. Decrease in pH, ATP:ADP ratio, ATP6AMP ratio, and K+:Na+ ratio were found to reduce the dog heart mitochondrial calcium uptake. It is likely that various factors such as pH, ATP:ADP ration, ATP:AMP ratio, and K+ :Na+ ration, in addition to damage in mitochondrial structure, play an important role in inhibiting mitochondrial calcium transport in failing hearts. The results also suggest that alterations in mitochondrial calcium transport are dependent upon the degree and type of heart failure.
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001386:Azides / Q000494:pharmacology; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D006224:Cricetinae; D001728:Dicumarol / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D004285:Dogs; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D008672:Metals, Alkali / Q000494:pharmacology; D008931:Mitochondria, Muscle / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D010210:Papillary Muscles / Q000473:pathology; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D000227:Adenine Nucleotides; D001386:Azides; D004140:Dinitrophenols; D008672:Metals, Alkali; D001728:Dicumarol; D002118:Calcium