Heparin inhibits the reconstituted plasma membrane Ca(2+)-ATPase from porcine brain synaptosome

Heparin has been shown to be involved in the regulation of cellular Ca(2+) by binding to many proteins with high affinity. Here we examined the effects of heparin on the plasma membrane Ca(2+)-ATPase from porcine brain synaptosome. Our results showed that heparin dramatically inhibited the ATP hydrolysis and Ca(2+) uptake in the presence and absence of calmodulin. Together with controlled proteolysis by trypsin, we concluded that the calmodulin-binding domain of the plasma membrane Ca(2+)-ATPase was less important for the heparin inhibition. Excess phosphatidylserine was able to eliminate the heparin inhibition. We observed that Ca(2+) affinity kept no obvious changes, but the ATP affinity of plasma membrane Ca(2+)-ATPase was apparently decreased in the presence of heparin. Our results indicated that heparin had little effects on ATP or Ca(2+) binding sites of the enzyme.