Intracellular calcium concentrations during "chemical hypoxia" and excitotoxic neuronal injury

Because hypoxic/ischemic neurodegeneration appears to be in part linked to glutamate neurotoxicity, we measured intracellular calcium (Ca2+i) levels in cultured hippocampal neurons during exposure to toxic doses of glutamate (GLU) and to an anoxic environment simulated by sodium cyanide (NaCN). Chan...

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Bibliographic Details
Published in:The Journal of neuroscience 1991-08, Vol.11 (8), p.2545-2551
Main Authors: Dubinsky, JM, Rothman, SM
Format: Article
Language:English
Subjects:
Animals
Biochemistry and metabolism
Biological and medical sciences
Calcium - metabolism
Central nervous system
Fundamental and applied biological sciences. Psychology
Glutamates - pharmacology
Glutamic Acid
Hypoxia - chemically induced
Hypoxia - metabolism
Intracellular Membranes - metabolism
Neurons - drug effects
Neurons - metabolism
Neurotoxins - pharmacology
Osmolar Concentration
Sodium Cyanide
Vertebrates: nervous system and sense organs
Citations: Items that cite this one
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Summary:Because hypoxic/ischemic neurodegeneration appears to be in part linked to glutamate neurotoxicity, we measured intracellular calcium (Ca2+i) levels in cultured hippocampal neurons during exposure to toxic doses of glutamate (GLU) and to an anoxic environment simulated by sodium cyanide (NaCN). Changes in Ca2+i produced by cyanide greatly exceeded those induced by GLU. The NaCN response was mimicked when oxidative metabolism was also disrupted by sodium azide, oligomycin, or dinitrophenol. Noncompetitive NMDA receptor antagonists and enzymatic GLU degradation abolished the GLU-induced Ca2+i increases and attenuated those produced by NaCN. Only NaCN-induced increases were blocked when dantrolene and ruthenium red were applied to prevent release from intracellular pools. All responses were reduced proportionally in the absence of added external calcium. These results suggest that extracellular GLU accumulation and subsequent activation of GLU receptors were involved in the NaCN response. During such metabolic compromise, however, GLU-induced elevations of Ca2+i were enormously amplified. In parallel toxicity studies, NaCN was not neurotoxic despite the large elevations in Ca2+i, indicating that a general elevation in cytoplasmic calcium does not necessarily predict neurodegeneration.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.11-08-02545.1991