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. (C) 2000 Academic Press.