The effect of Cd^2+, Pb^2+ and Hg^2+ on the Ca^2+-ATPase activity of sarcoplasmic reticulum from rabbit muscle was studied. The concentration of relevant free and complex species for the assay conditions have been computed. As a result, ATP hydrolysis was found to be inhibited with an IC(50) value of 950 nmol/l free Cd^2+ or 95 nmol/l free Pb^2+. Although calculation of the free Hg2+ was not possible, the comparison of the IC50 values for total metal ions show that Hg^2+ is the strongest inhibitor of enzyme activity. The inhibition by Cd^2+ seems to be independent of substrate concentration, whereas the inhibitory effect of Pb^2+ is lowered in the presence of higher MgATP concentrations. Our data illustrate that the three heavy metals are potent inhibitors of the Ca^2+ pump. Therefore low concentrations of these metal ions may disturb intracellular Ca^2+ homeostasis and act on Ca^2+-mediated cell functions.

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