EFFECTS OF CA(II) IONS ON MN(II) DYNAMICS IN CHICK GLIA AND RAT ASTROCYTES - POTENTIAL REGULATION OF GLUTAMINE-SYNTHETASE

Previous studies have demonstrated that in glia and astrocytes Mn(II) is distributed with ca. 30-40% in the cytoplasm, 60-70% in mitochondri a. Ca(II) ions were observed to alter both the flux rates and distribu tion of Mn(LI) ions in primary cultues of chick glia and rat astrocyte s. External (influxing) Ca(II) ions had the greatest effect on Mn(II) uptake and efflux, compared to internal (effluxing) or internal-extern al equilibrated Ca(II) ions. External (influxing) Ca(II) ions inhibite d the net rate and extent of Mn(II) uptake but enhanced Mn(II) efflux front mitochondria. These observations differ from Ca(II)-Mn(II) effec ts previously reported with ''brain'' (neuronal) mitochondria. Overall , increased cytoplasmic Ca(II) acts to block Mn(lI) uptake and enhance Mn(II) release by mitochondria, which serve to increase the cytoplasm ic concentration of free Mn(II). A hypothesis is presented involving e xternal L-glutamate acting through membrane receptors to mobilize cell Ca(II), which in turn causes mitochondrial Mn(II) to released. Becaus e the concentration of free cytoplasmic Mn(II) is poised near the K-d for Mn(II) with glutamine synthetase, a slight increase in cytoplasmic Mn(II) will directly enhance the activity of glutamine synthetase, wh ich catalyzes removal of neurotoxic glutamate and ammonia.