Neurotoxic glutamate treatment of cultured cerebellar granule cells induces Ca2+ -dependent collapse of mitochondrial membrane potential and ultrastructural alterations of mitochondria.
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 microM) in Mg2+-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 microM) and cobalt chloride (2 mM) prevented the deteriorative effects of glutamate. These data suggest that glutamate-induced Ca2+ overload of the neurons can lead to non-specific permeability of the inner mitochondrial membrane, resulting in neuronal death.
Isaev
N K
NK
Brain Research Institute, Russian Academy of Medical Sciences, Moscow, Russian Federation.
Zorov
D B
DB
Stelmashook
E V
EV
Uzbekov
R E
RE
Kozhemyakin
M B
MB
Victorov
I V
IV
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D003594:Cytoplasmic Granules / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D005456:Fluorescent Dyes; D018698:Glutamic Acid / Q000633:toxicity*; D008564:Membrane Potentials / Q000187:drug effects*; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D020112:Rhodamine 123; D012235:Rhodamines
D005456:Fluorescent Dyes; D012235:Rhodamines; D020112:Rhodamine 123; D018698:Glutamic Acid; D002118:Calcium