Glycolysis supports calcium uptake by the sarcoplasmic reticulum in skinned ventricular fibres of mice deficient in mitochondrial and cytosolic creatine kinase

Several works have shown the importance of the creatine kinase (CK) system for cardiac energetics and Ca2+ homeostasis. Nevertheless, CK-deficient mic e have cardiac function close to normal, at least under conditions of low o r moderate workload. To characterize possible adaptive changes of the sarco plasmic reticulum (SR) and potential role of glycolytic support in cardiac contractility we used the skinned fibre technique to study properties of th e SR and myofibrils, in control and muscle-type homodimer (MM-/mitochondria l-CK)-deficient mice. In control fibres, SR Ca2+ loading with ATP and phosp hocreatine (solution P-L) was significantly better than loading with ATP al one (solution A(L)), as determined by analysis of caffeine-induced tension transients. Loading in the presence of ATP and glycolytic intermediates (so lution G(L)) was not significantly different from solution P-L. These data indicate that Ca2+ uptake by the SR in situ depends on a local ATP:ADP rati o that is controlled by both CK and glycolytic enzymes. In CK-deficient mic e, Ca2+ loading was impaired in solution P-L due to the absence of CK. In s olution G(L), loading was significantly increased, such that calculated Ca2 + release parameters were normalized to those in control fibres in solution P-L. In CK-deficient mice, fibre kinetic parameters of tension recovery we re impaired after quick stretch in solution P-L and were not improved in so lution G(L). These results show that in CK-deficient mice, at least, under basal conditions, glycolysis can replace the CK system in fueling the SR Ca 2+ ATPase, but not the myosin ATPase, and may in part explain the limited p henotypic alterations seen in the hearts of these mice. (C) 2000 Academic P ress.