ALTERATION OF CA2- MODULATION BY SULFATED POLYSACCHARIDES AND TRIFLUOPERAZINE( FLUXES IN BRAIN MICROSOMES BY K+ AND NA+ )

Rat brain microsomes accumulate Ca2+ at the expense of ATP hydrolysis. The rate of transport is not modulated by the monovalent cations K+, Na+, or Li+. Both the Ca2+ uptake and the Ca2+-dependent ATPase activi ty of microsomes are inhibited by the sulfated polysaccharides heparin , fucosylated chondroitin sulfate, and dextran sulfate. Half-maximal i nhibition is observed with sulfated polysaccharide concentrations rang ing from 0.5 to 8.0 mu g/ml. The inhibition is antagonized by KCl and NaCl but not by LiCl. As a result, Ca2+ transport by the native vesicl es, which in the absence of polysaccharides is not modulated by monova lent cations, becomes highly sensitive to these ions. Trifluoperazine has a dual effect on the Ca2+ pump of brain microsomes. At low concent rations (20-80 mu M) it stimulates the rate of Ca2+ influx, and al con centrations > 100 mu M it inhibits both the Ca2+ uptake and the ATPase activity. The activation observed at low trifluoperazine concentratio ns is specific for the brain Ca2+-ATPase; for the Ca2+-ATPases found i n blood platelets and in the sarcoplasmic reticulum of skeletal muscle , trifluoperazine causes only a concentration-dependent inhibition of Ca2+ uptake. Passive Ca2+ efflux from brain microsomes preloaded with Ca2+ is increased by trifluoperazine (50-150 mu M), and this effect is potentiated by heparin (10 mu g/ml), even in the presence of KCl. It is proposed that the Ca2+-ATPase isoform from brain microsomes is modu lated differently by polysaccharides and trifluoperazine when compared with skeletal muscle and platelet isoforms.