Loading of calcium and strontium into the sarcoplasmic reticulum in rat ventricular muscle

Previous work suggests that strontium ions (Sr(2+)) are less effective than calcium ions (Ca(2+)) at supporting excitation-contraction (EC) coupling in cardiac muscle. We therefore tested whether this was due to differences in the uptake and release of Ca(2+)and Sr(2+)by the sarcoplasmic reticulum (SR) of rat ventricular trabeculae and myocytes at 22-24 degrees C. In permeabilized trabeculae, isometric contractions activated by exposure to Ca(2+)- and Sr(2+)-containing solutions produced similar maximal force, but were four times more sensitive to Ca(2+)than to Sr(2+). The rate of loading and maximal SR capacity for caffeine-releasable Ca(2+)and Sr(2+)were similar. In isolated, voltage-clamped ventricular myocytes, the SR content was measured as Na(+)-Ca(2+)exchange current during caffeine-induced SR cation releases. The SR Ca(2+)load reached a steady maximum during a train of voltage clamp depolarizations. A similar maximal Sr(2+)load was not observed, suggesting that the SR capacity for Sr(2+)exceeds that for Ca(2+). Therefore, the relative inability of Sr(2+)to support cardiac EC coupling appears not to be due to failure of the SR to sequester Sr(2+). Instead, increases in cytosolic [Sr(2+)] seem to poorly activate Sr(2+)release from the SR.