PHOSPHORYLATION POTENTIAL, ADENOSINE FORMATION, AND CRITICAL PO2 IN STIMULATED RAT CARDIOMYOCYTES

This study investigated the relationship between O-2 consumption ((V) over dot O-2) and energy status in isolated rat cardiomyocytes using a system in which O-2 supply (PO2) was maintained constant. For this pu rpose, Vet, phosphocreatine, ATP, intracellular pH, and adenosine of q uiescent and stimulated cardiomyocytes were measured while the ambient PO2 was clamped between 0.1 and 120 mmHg. In quiescent cardiomyocytes ((V) over dot O-2: 7.9 +/- 1.2 nmol.min(-1).mg protein(-1)), the thre shold below which respiration decreased (critical PO2) was 1.4 mmHg. A bove this value, energy status remained constant; below 1 mmHg, both f ree ADP and adenosine increased. Stimulation increased VO2 threefold a nd shifted the critical PO2 to 10 mmHg. Above this value, free ADP and adenosine remained unchanged; between 10 and 5 mmHg, (V) over dot O-2 was reduced but this did not change free ADP or adenosine. These find ings demonstrate that I)under well-oxygenated conditions (PO2 > 10 mmH g), (V) over dot O-2 is not controlled by ADP; 2) similarly, the adeno sine formation is independent of (V) over dot O-2; a PO2 <5 mmHg is a prerequisite for enhanced adenosine formation; and 3) when O-2 supply becomes limiting, ATP consumption is downregulated without measurable changes in energy status (hibernation).