Neurotoxic glutamate treatment of cultured cerebellar granule cells induces Ca2+‐dependent collapse of mitochondrial membrane potential and ultrastructural alterations of mitochondria

FEBS Letters

Zorov, Dmitry B.¹  Stelmashook, Elena V.²  Victorov, Ilya V.²  Uzbekov, Rustem E.¹  Isaev, Nikolaj K.²  Kozhemyakin, Maxim B.² 

[1] A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, 117292, Moscow, Russian Federation;Brain Research Institute, Russian Academy of Medical Sciences, p. Obuha 5, 103064, Moscow, Russian Federation

关键词: Mitochondria;    Glutamate;    Neurotoxicity;    Membrane potential;    Ultrastructure;    Cytosolic Ca2+;    GLU;    glutamate;    R123;    rhodamine 123;    BSM;    balanced salt medium;    MK-801;    (+)-5-methyl-10;    11-dihydro-5H-dibenzo(a;    d)cyclohepten-5;    10-imine hydrogen maleate;    NMDA;    N-methyl-d-aspartate;   

DOI  :  10.1016/0014-5793(96)00804-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 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 μM) 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.

【 授权许可】

Unknown