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Alteration of Ca 2+ Fluxes in Brain Microsomes by K + and Na + : Modulation by Sulfated Polysaccharides and Trifluoperazine
Author(s) -
Rocha Joao B. T.,
Wolosker Herman,
Souza Diogo O.,
De Meis Leopoldo
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.66020772.x
Subject(s) - trifluoperazine , sulfation , chemistry , microsome , modulation (music) , polysaccharide , biophysics , biochemistry , calcium , biology , physics , calmodulin , organic chemistry , enzyme , acoustics
Rat brain microsomes accumulate Ca 2+ at the expense of ATP hydrolysis. The rate of transport is not modulated by the monovalent cations K + , Na + , or Li + . Both the Ca 2+ uptake and the Ca 2+ ‐dependent ATPase activity of microsomes are inhibited by the sulfated polysaccharides heparin, fucosylated chondroitin sulfate, and dextran sulfate. Half‐maximal inhibition is observed with sulfated polysaccharide concentrations ranging from 0.5 to 8.0 µg/ml. The inhibition is antagonized by KCl and NaCl but not by LiCl. As a result, Ca 2+ transport by the native vesicles, which in the absence of polysaccharides is not modulated by monovalent cations, becomes highly sensitive to these ions. Trifluoperazine has a dual effect on the Ca 2+ pump of brain microsomes. At low concentrations (20–80 µ M ) it stimulates the rate of Ca 2+ influx, and at concentrations >100 µ M it inhibits both the Ca 2+ uptake and the ATPase activity. The activation observed at low trifluoperazine concentrations is specific for the brain Ca 2+ ‐ATPase; for the Ca 2+ ‐ATPases found in blood platelets and in the sarcoplasmic reticulum of skeletal muscle, trifluoperazine causes only a concentration‐dependent inhibition of Ca 2+ uptake. Passive Ca 2+ efflux from brain microsomes preloaded with Ca 2+ is increased by trifluoperazine (50–150 µ M ), and this effect is potentiated by heparin (10 µg/ml), even in the presence of KCl. It is proposed that the Ca 2+ ‐ATPase isoform from brain microsomes is modulated differently by polysaccharides and trifluoperazine when compared with skeletal muscle and platelet isoforms.