Dominant role of mitochondria in protection against a delayed neuronal Ca2+ overload induced by endogenous excitatory amino acids following a glutamate pulse

FEBS Letters

Khodorov, B.²  Vergun, O.²  Vinskaya, N.²  Pinelis, V.¹  Storozhevykh, T.¹ 

[1]Institute of Pediatrics, Russian Academy of Medical Sciences, Moscow, Russian Federation

[2]Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russian Federation

关键词: Mitochondrial Ca2+ uptake;    Ca2+ overload;    Endogenous excitatory amino acid;    Cultured neuron;    [Ca2+]i;    [Na+]i;    the cytosolic Ca2+;    Na+ concentrations;    respectively;    Fura-2/AM;    acetoxymethyl ester of fura-2;    HEPES;    4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid;    NMDA;    N-methy-d-aspartate;    GLU;    glutamate;    AP-5;    2-amino-5-phosphonopentanoic acid;    NMDG;    N-methy-d-glucamine;    HBSS;    HEPES-buffered salt solution;    ANT;    antimycin A;    OLIG;    oligomycin;    FCCP;    carbonyl cyanide p-trifluoromethoxyphenylhydrazone;    DCE;    delayed [Ca2+]i elevation;    EAA;    excitatory amino acids;   

DOI  :  10.1016/0014-5793(96)00873-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The objective of this study was to evaluate the contribution of mitochondria to the clearance of Ca²⁺ loads induced by glutamate or 25 mM K⁺ pulses. The mitochondrial Ca²⁺ 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 [Ca²⁺] _i recovery following a 1-min 100 μM glutamate pulse. However, the late slow phase of [Ca²⁺] _i recovery in the presence of mitochondrial poisons was transformed into a delayed [Ca²⁺] _i elevation culminating in the neuronal Ca²⁺ overload. Suppression of the Na⁺/Ca²⁺ exchange caused by glutamate-induced [Na⁺] _i elevation promoted the development of delayed Ca²⁺ increase. Under identical conditions, the high [Ca²⁺] _i transient induced by 25 mM K⁺ was never accompanied by a delayed Ca²⁺ elevation. The glutamate-induced delayed Ca²⁺ increase could be readily abolished by the removal of external Ca²⁺ 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 Ca²⁺ overload induced by endogenous excitatory amino acids released in response to a short-term glutamate challenge.

【 授权许可】

Unknown