Mitochondrial deenergization underlies neuronal calcium overload following a prolonged glutamate challenge

FEBS Letters

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

[1] Institute of Pediatrics, Moscow, Russian Federation;Institute of General Pathology and Pathophysiology, Baltiyskaya Str. 8, 125315 Moscow, Russian Federation

关键词: Mitochondrial depolarization;    Neuronal Ca2+ overload;    Glutamate neurotoxicity;    [Ca2+]i;    cytosolic Ca2+;    [Na+]i;    Na+ concentrations;    pHi;    cytosolic pH;    fura-2/AM;    acetoxymethyl ester of fura-2;    NMDA;    N-methyl-d-aspartate;    GLU;    glutamate;    NMDG;    N-methyl-d-glucamine;    HBSS;    HEPES-buffered salt solution;    FCCP;    carbonyl cyanide p-trifluoromethoxyphenylhydrazone;    V mit;    mitochondrial potential;    MD;    mitochondrial depolarization;   

DOI  :  10.1016/S0014-5793(96)01139-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The purpose of our work was to study the relationship between glutamate (GLU)-induced mitochondrial depolarization and deterioration of neuronal Ca²⁺ homeostasis following a prolonged GLU challenge. The experiments were performed on cultured rat cerebellar granule cells using the fluorescent probes, rhodamine 123 and fura-2. All the cells, in which 100 μM GLU ( 10 μM glycine, 0 Mg²⁺) induced only relatively slight mitochondrial depolarization (1.1-1.3-fold increase in rhodamine 123 fluorescence), retained their ability to recover [Ca²⁺]_i following a prolonged GLU challenge. In contrast, the cells in which GLU treatment induced pronounced mitochondrial depolarization (2–4-fold increase in rhodamine 123 fluorescence), exhibited a high Ca²⁺ plateau in the post-glutamate period. Application of 3–5 mM NaCN or 0.25–1 μM FCCP during this Ca²⁺ plateau phase usually failed to produce a further noticeable increase in [Ca²⁺]₁. Regression analysis revealed a good correlation (r ² = 0.88 ± 0.03, n = 19) between the increase in the percentage of rhodamine 123 fluorescence and the postglutamate [Ca²⁺]_i Collectively, the results obtained led us to conclude that the GLU-induced neuronal Ca²⁺ overload was due to the collapse of the mitochondrial potential and subsequent ATP depletion.

【 授权许可】

Unknown