Stimulatory effect of calcium chelators on Na+-Ca2+ exchange in cardiac sarcolemmal vesicles

The calcium chelators EGTA, EDTA and cyclohexanediamine tetraacetic acid (CDTA) enhance initial rates of Nai+-dependent Ca2+ uptake by cardiac sarcolemmal vesicles. The affinity of the exchanger for calcium is increased in the presence of the chelators to an extent dependent on chelator concentration and on the range of free calcium concentrations over which the phenomenon is measured. For free Ca2+ in the range of 4 muM or less, the apparent Km is lowered to approximately 1 muM. The Ca-chelator complex appears to be the species which causes stimulation. The effect is not due to sequestration of contaminating heavy metal ions in the sarcolemmal membrane preparations or the solutions used in experiments. Caution is suggested in the use of EGTA or EDTA as calcium buffers when measuring calcium dependence of phenomena involving calcium binding and transport, because the added chelator may alter the properties of the system.