Dhalla N S, Tomlinson C W, Yates J C, Lee S L, Varley K G, Borowski I F, Barwinsky J
Recent Adv Stud Cardiac Struct Metab. 1975;5:177-87.
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.
与狗、兔和仓鼠心脏的对照值相比，衰竭的人类心脏中的线粒体钙摄取（而非结合），如同微粒体钙摄取一样，有所减少。在遗传性肌病仓鼠（BIO 14.6）充血性心力衰竭的早期、中期和晚期，均观察到线粒体钙结合和摄取减少。线粒体钙转运抑制剂双香豆素、二硝基酚和叠氮化钠，可使离体大鼠心脏的收缩力迅速下降。大鼠心脏在无钠或无钾培养基灌注时无法产生收缩力，这与线粒体钙摄取增加有关。在无钙培养基后用对照培养基灌注大鼠心脏时，观察到线粒体钙摄取显著增加。在急性缺血的犬心肌或收缩力严重降低的低氧大鼠心脏中，未发现线粒体钙摄取有变化。用无底物培养基灌注大鼠心脏时，线粒体钙转运和收缩力均降低；然而，钙摄取的变化继发于收缩力的下降。发现pH值、ATP:ADP比值、ATP:AMP比值和K+:Na+比值的降低会减少犬心脏线粒体钙摄取。除了线粒体结构受损外，诸如pH值、ATP:ADP比值、ATP:AMP比值和K+:Na+比值等各种因素，可能在抑制衰竭心脏中的线粒体钙转运方面起重要作用。结果还表明，线粒体钙转运的改变取决于心力衰竭的程度和类型。
