Control of Energy Transport in Cardiac Muscle

Abstract

The research of the mechanism of energy supply for contraction has reached a stage when the importance of coupled creatine kinase (CK) reactions in energy transport (1, 2) is studied in vivo by using ³¹P-NMR technique (3–6). Especially decisive may be a combination of this method with depletion of phosphocreatine and creatine stores by feeding experimental animals with guanidinopropionate, an analog of creatine which is not used rapidly in the creatine kinase reaction (1–4). By now, however, the use of these approaches has caused only confusions: several groups have reached a conclusion of the nonimportance of the coupled creatine kinase reactions (3, 4), in spite of abundant biochemical and physiological evidence (1, 2) and in contrast with other groups who have found good evidence for phosphocreatine shuttle by using a ³¹P-NMR technique (5, 6). This has even led Bessman to conclude that “the discrepancies above indicate the serious technical problems that beset NMR measurements to date” (2). Obviously, in this situation very careful performance and critical analysis of the ³¹P-NMR experiments under various conditions of heart function by several independent groups of investigators is vitally important to establish the true course of events in heart cells. In the current work we describe the results obtained in our laboratories in ³¹P-NMR studies of the effect of ATP and phosphocreatine depletion on heart function, and also analyse the important question of the influence of physiological ion composition of solution on the coupled CK reaction in mitochondria.