Intracellular calcium concentration during hypoxia and metabolic inhibition in mammalian ventricular muscle.

Papillary muscles from rats, cats and ferrets were microinjected with aequorin, a photoprotein which emits light as a function of Ca2+ concentration. The effects of hypoxia and different types of metabolic inhibition on intracellular Ca2+ concentration ([ Ca2+]i) and tension were studied. 2. Exposure of the muscle to hypoxia (PO2 less than 5 mmHg) or CN- caused a reversible decrease in developed tension, with no change in the magnitude of the Ca transient associated with each contraction. The rate of decline of the Ca transient was decreased slightly but significantly during these interventions. 3. In half the preparations examined, the initial fall in tension produced by hypoxia was interrupted by a short-lived increase in developed tension. No change in the Ca transient was associated with this increase in tension. 4. After exposure of papillary muscles to glucose-free Tyrode solution for short periods (less than 1 hr), hypoxia and CN- had a similar effect on the magnitude of the light transient and developed tension to section 2 above. After perfusion with glucose-free Tyrode solution for longer periods (greater than 2 hr), hypoxia and CN- caused a greater decrease in developed tension and a marked decrease in the magnitude of the Ca transient. 5. The addition of CN- to papillary muscles which were superfused with Tyrode solution containing 2-deoxyglucose instead of glucose, caused a rapid decrease in the magnitude of the Ca transient and of developed tension. These changes were not fully reversible. 6. In muscles which developed an hypoxic contracture, the resting [Ca2+]i did not rise by more than a factor of 1.4. 7. It is concluded that when glycolysis can proceed, inhibition of oxidative phosphorylation results in a decrease in developed tension with no change in the magnitude of the Ca transient. This decrease in the apparent sensitivity of the contractile proteins to Ca2+ is attributable to the decrease in intracellular pH known to occur in this situation. There may also be a second mechanism tending to reduce the Ca transient under these conditions. 8. During inhibition of glycolysis and oxidative phosphorylation, developed tension falls as a result of decreased Ca transients. This could be because the free energy of hydrolysis of ATP falls below the level required to pump Ca from the myoplasm to the sarcoplasmic reticulum.