Mechanisms Underlying Glutamate-induced Swelling of Astrocytes in Primary Culture

  • P. H. Chan
  • L. Chu
Conference paper
Part of the Acta Neurochirurgica book series (NEUROCHIRURGICA, volume 51)


The effects of glutamate and its agonists and antagonists on the swelling of primary astrocytes were studied. Glutamate, aspartate, homocysteate, and quisqualate caused a significant increase in astrocytic swelling as measured by 3-0-methyl-[14C]-glucose uptake and by phase-contrast microscopic observations. N-methyl-D-aspartate and kainate were not effective, nor were the competitive NMDA receptor antagonists. Ketamine and MK-801, the non-competitive NMDA receptor antagonists protected the cultured astrocytes against glutamate-induced swelling. Moreover, Glu-induced astrocytic swelling was significantly reduced when sodium-ions were depleted from the culture medium. The sodium ion dependence of Glu-induced astrocytic swelling is rather specific, since depletion of Ca2+ or Mg2+ had no effect. Our data suggest that Na+-dependent, Glu-mediated cell swelling occurs in primary cell cultures of astrocytes.


NMDA Receptor NMDA Receptor Antagonist Primary Cell Culture Primary Astrocyte Noncompetitive NMDA Receptor Antagonist 
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  1. 1.
    Bowman CL, Kimelberg HK (1984) Excitatory amino acid directly depolarizes rat brain astrocytes in primary culture. Nature 311: 656–659PubMedCrossRefGoogle Scholar
  2. 2.
    Chan PH, Fishman RA, Lee JL, Candelise L (1979) Effects of excitatory neurotransmitter amino acids on swelling of rat brain cortical slices. J Neurochem 33: 1309–1315PubMedCrossRefGoogle Scholar
  3. 3.
    Chan PH, Chu L (1989) Ketamine protects cultured astrocytes from glutamate-induced swelling. Brain Res 487: 380–383PubMedCrossRefGoogle Scholar
  4. 4.
    Chan PH, Chu L, Chen S (1990) Effects of MK-801 on glutamate-induced swelling of astrocytes in primary cell culture. J Neurosci Res 25: 87–93PubMedCrossRefGoogle Scholar
  5. 5.
    Choi DW (1987) Ionic dependence of glutamate neurotoxicity. J Neurosci 7: 369–379PubMedGoogle Scholar
  6. 6.
    Choi DW, Koh J-Y, Peters S (1988) Pharmacology of glutamate neurotoxicity in cortical cell culture: Attenuation by NMDA antagonists. J Neurosci 8: 185–196PubMedGoogle Scholar
  7. 7.
    Kimelberg HK (1987) Anisotonic media and glutamate-induced ion transport and volume responses in primary astrocyte cultures. J Physiol (Paris) 82: 294–303Google Scholar
  8. 8.
    Kimelberg HK, Ransom BR (1986) Physiological and pathological aspects of astrocytic swelling. In: Federoff S, Vernadakis A (eds) Astrocytes, vol 3. Academic Press, Orlando, FL, pp 129–166Google Scholar
  9. 9.
    Kletzien RF, Pariza MW, Becker JE, Patter VR (1975) A method using 3–0-methyl-D-glucose and phloretin for the determination of intracellular water space of cells in monolayer culture. Anal Biochem 68: 537–544PubMedCrossRefGoogle Scholar
  10. 10.
    Rothman S (1984) Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death. J Neurosci 4: 1884–1891PubMedGoogle Scholar
  11. 11.
    Rothman SM, Olney JW (1986) Glutamate and pathophysiology of hypoxic-ischaemic brain damage. Ann Neurol 19: 105–111PubMedCrossRefGoogle Scholar
  12. 12.
    Simon RP, Swan JH, Griffiths T, Meldrum BS (1984) Blockade of N-methyl-D-aspartate receptors may protect against ischaemic damage in the brain. Science 226: 850–852PubMedCrossRefGoogle Scholar
  13. 13.
    Sontheimer H, Kettenmann H, Backus KH, Schachner M (1988) Glutamate opens Na’ /K+ channels in cultured astrocytes. Glia 1: 328–336PubMedCrossRefGoogle Scholar
  14. 14.
    Wieloch T (1985) Hypoglycaemia-induced neuronal damage prevented by an N-methyl-D-aspartate antagonist. Science 230: 681–683PubMedCrossRefGoogle Scholar
  15. 15.
    Yu ACH, Chan PH, Fishman RA (1986) Effects of arachidonic acid on glutamate and gamma-aminobutyric acid uptake in primary cultures of rat cerebral cortical astrocytes and neurons. J Neurochem 47: 1181–1189PubMedCrossRefGoogle Scholar
  16. 16.
    Yu ACH, Gregory GA, Chan PH (1989) Hypoxia-induced dysfunctions and injury of astrocytes in primary cell cultures. J Cereb Blood Flow Metab 9: 20–28PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • P. H. Chan
    • 1
  • L. Chu
    • 1
  1. 1.CNS Injury and Edema Center, Department of Neurological Surgery and NeurologySchool of Medicine, University of CaliforniaSan FranciscoUSA

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