The lack of extracellular Na+ exacerbates Ca2+‐dependent damage of cultured cerebellar granule cells

FEBS Letters

Zorov, Dmitry B²  Alexandrova, Olga P³  Andreeva, Nadezhda A³  Victorov, Ilya V³  Isaev, Nikolaj K²  Polyakova, Irina A¹  Stelmashook, Elena V³ 

[1]Faculty of Biology, Moscow State University, Moscow, Russia

[2]A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119899, Russia

[3]Brain Research Institute, Russian Academy of Medical Sciences, Moscow, Russia

关键词: Neuron;    Glutamate;    Mitochondria;    Na+/Ca2+ exchange;    Membrane potential;    Ultrastructure;    R123;    rhodamine 123;    MK-801;    (+)-5-methyl-10;    11-dihydro-5H-dibenzo(a;    d)cyclohepten-5;    10-imine hydrogen maleate;    NMDA;    N-methyl-d-aspartate;    BSM;    balanced salt medium;    SBSM;    sucrose balanced salt medium;    APH;    d;    l-2-amino-7-phosphonoheptanoate;   

DOI  :  10.1016/S0014-5793(98)00979-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Rhodamine 123 staining, light and electron microscopy were used to evaluate the ultrastructural and functional state of cultured cerebellar granule cells after short treatment with the solution where NaCl was substituted by sucrose (sucrose balance salt medium, SBSM). Cell exposure to SBSM for 20 min resulted in the fact that mitochondria in the neurons lost their ability to sequester rhodamine 123. This effect could be prevented by: (i) non-competitive N-methyl-d-aspartate (NMDA) receptor channel blocker, 10⁻⁵ M MK-801; (ii) a competitive specific antagonist of NMDA glutamate receptors, 0.25×10⁻³ M d,l-2-amino-7-phosphonoheptanoate (APH); (iii) 10⁻³ M cobalt chloride; (iv) removal of Ca²⁺ from the medium. Low Na⁺ in the Ca²⁺-containing medium caused considerable mitochondrial swelling in granule cells. However, the same treatment in the absence of calcium ions in the medium abolished the deleterious effect of SBSM on the neuronal mitochondrial structure and functions. It is suggected that (i) the exposure of cultured cerebellar granule cells to SBSM leads to a release of endogenous glutamate from cells; (ii) Ca²⁺ ions potentially de-energizing neuronal mitochondria enter the neuron preferentially through the NMDA channels rather than through the Na⁺/Ca²⁺ exchanger; (iii) mitochondrial swelling in granule cells is highly Ca²⁺-dependent; (iv) cellular overload with sodium ions can activate mitochondrial Na⁺/Ca²⁺ exchanger and thus prevent permeability transition pore opening in mitochondria.

【 授权许可】

Unknown