Ruthenium red and caffeine affect the Ca2+-ATPase of the sarcoplasmic reticulum

Effects of ruthenium red and caffeine (a Ca2+ release blocker and an inducer, respectively) on Ca2+ uptake by sarcoplasmic reticulum (SR) vesicles and formation of the phosphorylated intermediate (EP) of the Ca2+-ATPase were studied using fast-kinetic techniques. Ruthenium red increased the rate and the maximum level of EP formation, while caffeine decreased both. Similarly, ruthenium red accelerated rapid Ca2+ uptake, while caffeine inhibited it. These drugs affected EP formation also with detergent solubilized Ca2+-ATPase. The concentrations required for half maximal effects on these functions (0.2 microM ruthenium red, 1.0 mM caffeine) are about the same as those for altering Ca2+ release. These results indicate that these reagents affect both the Ca2+-pump as well as the Ca2+ release mechanism, suggesting that the Ca2+-pump and Ca2+ release have some mechanisms in common.