Cellular and Molecular Neurobiology

, Volume 14, Issue 6, pp 637–652 | Cite as

Astrocytes as potential modulators of mercuric chloride neurotoxicity

  • M. Aschner
  • K. J. Mullaney
  • M. N. Fehm
  • D. E. WagonerJr.
  • D. Vitarella
Article

Summary

1. MC has been shown to inhibit the uptake ofl-glutamate and increased-aspartate release from preloaded astrocytes in a dose-dependent fashion.

2. Two sulfhydryl (SH-)-protecting agents; reduced glutathione (GSH), a cell membrane-nonpenetrating compound, and the membrane permeable dithiothreitol (DTT), have been shown consistently to reverse the above effects. MC-inducedd-aspartate release is completely inhibited by the addition of 1 mM DTT or GSH during the actual 5-min perfusion period with MC (5µM); when added after MC treatment, DTT fully inhibits the MC-inducedd-aspartate release, while GSH does not.

3. Neither DTT nor GSH, in the absence of MC, have any effect on the rate of astrocyticd-aspartate release. Other studies demonstrate that although MC treatment (5µM) does not induce astrocytic swelling, its addition to astrocytes swollen by exposure to hypotonic medium leads to their failure to volume regulate.

4. Omission of calcium from the medium greatly potentiates the effect of MC on astrocyticd-aspartate release, an effect which can be reversed by cotreatment of astrocytes with the dihydropyridine Ca2+-channel antagonist nimodipine (10µM), indicating that one possible route of MC entry into the cells is through voltage-gated L-type channels.

Key words

mercuric chloride l-glutamate d-aspartate astrocytes thiols (-SH) 

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Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • M. Aschner
    • 1
  • K. J. Mullaney
    • 1
  • M. N. Fehm
    • 1
  • D. E. WagonerJr.
    • 1
  • D. Vitarella
    • 1
  1. 1.Department of Pharmacology and Toxicology, A-136Albany Medical CollegeAlbany

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