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Mitochondrial deenergization underlies neuronal calcium overload following a prolonged glutamate challenge
Author(s) -
Khodorov B.,
Pinelis V.,
Vergun O.,
Storozhevykh T.,
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/s0014-5793(96)01139-8
Subject(s) - depolarization , glutamate receptor , rhodamine 123 , mitochondrion , rhodamine , biophysics , calcium , chemistry , membrane potential , homeostasis , fluorescence , biology , biochemistry , endocrinology , physics , receptor , organic chemistry , quantum mechanics , multiple drug resistance , antibiotics
The purpose of our work was to study the relationship between glutamate (GLU)‐induced mitochondrial depolarization and deterioration of neuronal Ca 2+ 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 Mg 2+ ) induced only relatively slight mitochondrial depolarization (1.1‐1.3‐fold increase in rhodamine 123 fluorescence), retained their ability to recover [Ca 2+ ] 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 Ca 2+ plateau in the post‐glutamate period. Application of 3–5 mM NaCN or 0.25–1 μM FCCP during this Ca 2+ plateau phase usually failed to produce a further noticeable increase in [Ca 2+ ] 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 [Ca 2+ ] i Collectively, the results obtained led us to conclude that the GLU‐induced neuronal Ca 2+ overload was due to the collapse of the mitochondrial potential and subsequent ATP depletion.