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Neurotoxic glutamate treatment of cultured cerebellar granule cells induces Ca 2+ ‐dependent collapse of mitochondrial membrane potential and ultrastructural alterations of mitochondria
Author(s) -
Isaev Nikolaj K.,
Zorov Dmitry B.,
Stelmashook Elena V.,
Uzbekov Rustem E.,
Kozhemyakin Maxim B.,
Victorov Ilya V.
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)00804-6
Subject(s) - glutamate receptor , mitochondrion , endoplasmic reticulum , ultrastructure , granule (geology) , rhodamine 123 , microbiology and biotechnology , nmda receptor , biology , membrane potential , biophysics , chemistry , biochemistry , receptor , anatomy , multiple drug resistance , antibiotics , paleontology
Rhodamine 123 staining and electron microscopy were used to reveal a correlation between the ultrastructural and functional state of cultured cerebellar granule cells after short glutamate treatment. Glutamate exposure (15 min, 100 μM) in Mg 2+ ‐free solution caused considerable ultrastructural alterations in a granule cell: clumping of the chromatin, swelling of the endoplasmic reticulum and mitochondria, and disruption of the mitochondrial cristae. After glutamate treatment, the mitochondria of the neurons lost their ability to sequester rhodamine 123. Both the N ‐methyl‐ d ‐aspartate receptor channel blocker MK‐801 (30 μM) and cobalt chloride (2 mM) prevented the deteriorative effects of glutamate. These data suggest that glutamate‐induced Ca 2+ overload of the neurons can lead to non‐specific permeability of the inner mitochondrial membrane, resulting in neuronal death.