Short‐term block of Na+/K+‐ATPase in neuro‐glial cell cultures of cerebellum induces glutamate dependent damage of granule cells

FEBS Letters

Weih, M.³  Stelmashook, E.V.¹  Zorov, D.²  Isaev, N.²  Dirnagl, U.³  Victorov, I.¹ 

[1] Brain Research Institute, Russian Academy of Medical Sciences, p. Obuha 5, Moscow 103064, Russia;A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119899, Russia;Department of Neurology, Charity Hospital, Humboldt University, Berlin, Germany

关键词: Ouabain;    Glutamate;    Na+/K+-ATPase;    Mitochondria;    Membrane potential;    Glu;    glutamate;    R123;    rhodamine 123;    Ou;    ouabain;    BSS;    balanced salt solution;    LiBSS;    balanced salt solution where potassium ions were substituted for lithium;    APH;    D;    L-2-amino-7-phosphonoheptanoate;    NMDA;    N-methyl-D-aspartate;   

DOI  :  10.1016/S0014-5793(99)00922-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Granule cells in a dissociated neuro-glial cell culture of cerebellum when exposed to ouabain (10⁻³ M) for 25 min apparently swell, increase their [Ca²⁺]_i with obvious depolarization of the mitochondrial membrane. In 3 h after ouabain was omitted from the solution, 62±3% of granule cells had pycnotic nuclei. The supplement of a solution with competitive specific antagonist of NMDA receptors, L-2-amino-7-phosphonoheptanoate (10⁻⁴ M, APH) together with ouabain prevented cells from swelling, mitochondrial deenergization, neuronal death and increase of [Ca²⁺]_i. These data suggest that cellular Na⁺/K⁺-ATPase inactivation in neuro-glial cell cultures of cerebellum leads to glutamate (Glu) accumulation, hyperstimulation of glutamate receptors, higher Ca²⁺ and Na⁺ influxes into the cells through the channels activated by Glu. This process leads to cell swelling, mitochondrial deenergization and death of granule cells. Possibly, the decrease of Na⁺/K⁺-ATPase activity in brain cells can lead to the onset of at least some chronic neurological disorders.

【 授权许可】

Unknown