Compartmentation of cellular calcium in rabbit ventricle dependent upon its transsarcolemmal route

Augmentation of calcium influx may be buffered in the myocardium by slowly exchangeable compartments. Myocardial calcium influx was enhanced in rabbit interventricular septa by interventions which affect either calcium channel current (BAY k 8644) or Na/Ca exchange (ouabain, low Na0). The effect of these interventions on slowly exchangeable calcium was measured by performing 45Ca washouts. In addition, beating was resumed following a period of prolonged quiescence and the effect on slowly exchangeable calcium measured. Previous work had shown that at a Ca0 of 1.0 mM, low sodium perfusion induced a significant increment in slowly exchangeable calcium. The present investigation demonstrates that ouabain and resumption of stimulation following quiescence also augment this calcium. At 1.0 mM Ca0, as few as 15 beats administered in a 10 min interval were found to induce a significant increment in calcium content, which could be inhibited by the mitochondrial inhibitor CCCP but not by ryanodine. In contrast, BAY k 8644 did not augment slowly exchangeable calcium, although it produced at 0.5 mM Ca0 the same inotropic response as ouabain and 75 mM Na0. In conclusion, slowly exchangeable calcium is not affected by augmentation of calcium channel current, but is enhanced by ouabain, resumption of stimulation, and low Na0. A common characteristic shared by those interventions which enhance slowly exchangeable calcium is an increased Nai/Na0 ratio, which results in an augmented calcium uptake via on Na/Ca exchange.