Uncoupling of muscle and blood platelets Ca2+ transport ATPases by heparin. Regulation by K+.

Heparin (1-10 micrograms/ml) inhibits the Ca2+ transport ATPases found in the sarcoplasmic reticulum of skeletal muscle, the plasma membrane of red cells, and the dense tubular system of blood platelets, but not the (Na+ + K+)-ATPase or the mitochondrial F1-ATPase. In the reversal of the Ca2+ pump, heparin uncouples the synthesis of ATP from Ca2+ efflux and inhibits the phosphorylation of the sarcoplasmic reticulum Ca(2+)-ATPase by Pi, but has no effect the phosphorylation by ATP. The effect of heparin on the muscle Ca(2+)-ATPase is abolished by KCl and NaCl (100 mM) and to a lesser extent by LiCl. These monovalent cations are not effective as antagonists of heparin on the platelet Ca(2+)-ATPase. The effects of heparin are antagonized by the polyamines spermine, spermidine, and ruthenium red. Unlike KCl, polyamines are equally effective in counteracting the effects of heparin in both muscle and platelet Ca(2+)-ATPases. In addition to heparin, the Ca(2+)-ATPases of muscle and blood platelets are also inhibited by dextran sulfate and fucose-branched chondroitin sulfate. The inhibition promoted by these glycosaminoglycans is antagonized by monovalent cations and polyamines in the same manner as heparin. Heparan sulfate, chondroitin sulfate, and hyaluronic acid have not effect on the Ca(2+)-ATPases studied.