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A role for Na + ‐dependent Ca 2+ extrusion in protection against neuronal excitotoxicity
Author(s) -
Mattson Mark P.,
Guthrie P. B.,
Kater S. B.
Publication year - 1989
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.3.13.2572500
Subject(s) - excitotoxicity , extracellular , calcium , glutamate receptor , hippocampal formation , neurotoxicity , chemistry , biophysics , calcium in biology , microbiology and biotechnology , neuron , intracellular , biochemistry , neuroscience , biology , toxicity , receptor , organic chemistry
The hypothesis that Na + ‐dependent calcium extrusion is important in protecting against neuronal excitotoxicity was tested. In cocultures of embryonic rat hippocampal neurons and mouse neuroblastoma hybrid (NCB‐20) cells, calcium ionophore A23187 (1 μM) or high levels of extracellular K + killed hippocampal neurons selectively, leaving NCB‐20 cells unscathed. Hippocampal neurons showed large, sustained rises in intracellular calcium in response to A23187 or K + , whereas NCB‐20 cells showed only transient calcium responses. The abilities of NCB‐20 cells to reduce the calcium load and to survive exposure to A23187 or K + were dependent on extracellular Na + , suggesting that an active Na + /Ca 2+ exchange mechanism was important in protecting against cell death. Finally, removal of extracellular Na + reduced the threshold for glutamate neurotoxicity in hippocampal neurons, demonstrating the importance of Na + /Ca 2+ exchange in protecting against excitotoxicity. Taken together, these findings suggest that differences in cell calcium‐regulating systems may determine whether a neuron lives or degenerates in the face of an excitatory challenge.—M attson , M. P.; G uthrie , P. B.; K ater , S. B. A role for Na + ‐dependent Ca 2+ extrusion in protection against neuronal excitotoxicity. FASEB J. 3: 2519‐2526; 1989.