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Dominant role of mitochondria in protection against a delayed neuronal Ca 2+ overload induced by endogenous excitatory amino acids following a glutamate pulse
Author(s) -
Khodorov B.,
Pinelis V.,
Storozhevykh T.,
Vergun O.,
Vinskaya N.
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)00873-3
Subject(s) - endogeny , glutamate receptor , excitatory amino acid transporter , excitatory postsynaptic potential , mitochondrion , amino acid , chemistry , pulse (music) , glutamic acid , biochemistry , microbiology and biotechnology , biology , receptor , detector , electrical engineering , engineering
The objective of this study was to evaluate the contribution of mitochondria to the clearance of Ca 2+ loads induced by glutamate or 25 mM K + pulses. The mitochondrial Ca 2+ uptake was suppressed by application of 0.5 μM antimycin A or 3–5 mM NaCN in combination with 2.5 μg/ml oligomycin. In most cells such treatments both in the presence and in the absence of external Na + failed to abolish the early fast phase of [Ca 2+ ] i recovery following a 1‐min 100 μM glutamate pulse. However, the late slow phase of [Ca 2+ ] i recovery in the presence of mitochondrial poisons was transformed into a delayed [Ca 2+ ] i elevation culminating in the neuronal Ca 2+ overload. Suppression of the Na + /Ca 2+ exchange caused by glutamate‐induced [Na + ] i elevation promoted the development of delayed Ca 2+ increase. Under identical conditions, the high [Ca 2+ ] i transient induced by 25 mM K + was never accompanied by a delayed Ca 2+ elevation. The glutamate‐induced delayed Ca 2+ increase could be readily abolished by the removal of external Ca 2+ or by application in the post‐glutamate period of the antagonist of NMDA receptors, 100–200 μM AP‐5. The results obtained suggest that mitochondria play a dominant role in the protection against the neuronal Ca 2+ overload induced by endogenous excitatory amino acids released in response to a short‐term glutamate challenge.