Loading of Calcium and Strontium into the Sarcoplasmic Reticulum in Rat Ventricular Muscle

Previous work suggests that strontium ions (Sr2+) are less effective than calcium ions (Ca2+) at supporting excitation–contraction (EC) coupling in cardiac muscle. We therefore tested whether this was due to differences in the uptake and release of Ca2+and Sr2+by the sarcoplasmic reticulum (SR) of rat ventricular trabeculae and myocytes at 22–24°C. In permeabilized trabeculae, isometric contractions activated by exposure to Ca2+- and Sr2+-containing solutions produced similar maximal force, but were four times more sensitive to Ca2+than to Sr2+. The rate of loading and maximal SR capacity for caffeine-releasable Ca2+and Sr2+were similar. In isolated, voltage-clamped ventricular myocytes, the SR content was measured as Na+–Ca2+exchange current during caffeine-induced SR cation releases. The SR Ca2+load reached a steady maximum during a train of voltage clamp depolarizations. A similar maximal Sr2+load was not observed, suggesting that the SR capacity for Sr2+exceeds that for Ca2+. Therefore, the relative inability of Sr2+to support cardiac EC coupling appears not to be due to failure of the SR to sequester Sr2+. Instead, increases in cytosolic [Sr2+] seem to poorly activate Sr2+release from the SR.