Effects of Ca(II) ions on Mn(II) dynamics in chick glia and rat astrocytes: Potential regulation of glutamine synthetase |
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Authors: | Frederick C Wedler Michael C Vichnin Brenda W Ley Georges Tholey Marc Ledig Jean-Christoph Copin |
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Institution: | (1) Biochemistry Program, Dept. of Molecular & Cell Biology, Althouse Laboratory, The Pennsylvania State University, 16802 University Park, Pennsylvania;(2) LNO-CNRS, Centre de Neurochimie, Universite L. Pasteur, 5 rue Bl. Pascal, F-67000 Strasbourg, France |
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Abstract: | Previous studies have demonstrated that in glia and astrocytes Mn(II) is distributed with ca. 30–40% in the cytoplasm, 60–70% in mitochondria. Ca(II) ions were observed to alter both the flux rates and distribution of Mn(II) ions in primary cultues of chick glia and rat astrocytes. External (influxing) Ca(II) ions had the greatest effect on Mn(II) uptake and efflux, compared to internal (effluxing) or internal-external equilibrated Ca(II) ions. External (influxing) Ca(II) ions inhibited the net rate and extent of Mn(II) uptake but enhanced Mn(II) efflux from mitochondria. These observations differ from Ca(II)–Mn(II) effects previously reported with brain (neuronal) mitochondria. Overall, increased cytoplasmic Ca(II) acts to block Mn(II) uptake and enhance Mn(II) release by mitochondria, which serve to increase the cytoplasmic concentration of free Mn(II). A hypothesis is presented involving external L-glutamate acting through membrane receptors to mobilize cell Ca(II), which in turn causes mitochondrial Mn(II) to be released. Because the concentration of free cytoplasmic Mn(II) is poised near the Kd for Mn(II) with glutamine synthetase, a slight increase in cytoplasmic Mn(II) will directly enhance the activity of glutamine synthetase, which catalyzes removal of neurotoxic glutamate and ammonia. |
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Keywords: | Manganese (II) ions Ca(II) ions effects of glutamine synthetase trace metals L-glutamate metabolism regulation of glia astrocytes |
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