Role of Na+/Ca2+ exchange in regulation of neuronal Ca2+ homeostasis requires re‐evaluation

FEBS Letters

Khodorov, B²  Grigortsevich, N²  Sorokina, E¹  Storozhevykh, T¹  Vinskaya, N¹  Vergun, O²  Pinelis, V¹ 

[1]Institute of Pediatrics, Russian Academy of Medical Sciences, Moscow, Russia

[2]Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia

关键词: Neurotoxicity;    Glutamate;    Na+/Ca2+ exchange;    Cultured neuron;    [Ca2+]i and [Na+]i;    cytosolic Ca2+ and Na+ concentrations;    FURA-2 AM;    FURA-2 acetoxymethyl ester;    BCECF-AM;    2′;    7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester;    Ara-C;    cytosine arabinoside;    HEPES;    4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid;    (+/−)-CPP;    (+/−)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid;    NMDA;    N-methyl-d-aspartate;    Glu;    glutamate;    AP-5;    2-amino-5-phosphonopentanoic acid;    Mem;    memantine;    Mon;    monensin;    NMDG;    N-methyl-d-glucamine;    HBSS;    HEPES-buffered salt solution;    CaR;    [Ca2+]i response;   

DOI  :  10.1016/S0014-5793(98)00758-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In cultured rat cerebellar granule cells an inhibition of plasma membrane Na⁺/Ca²⁺ exchange by removal of external Na⁺ (replacement with NMDG) caused an increase in [Ca²⁺]_i at rest and a considerable delay in [Ca²⁺]_i recovery from Glu-imposed [Ca²⁺]_i load. These effects did not result from Ca²⁺ influx through reversed Na⁺/Ca²⁺ exchange since they were readily abolished or prevented by using the NMDA receptor inhibitor AP-5 (100 μM) or the NMDA channel blocker memantine (25–50 μM). The effect of Na⁺/NMDG replacement could be enhanced by: (1) an increase in cytoplasmic Na⁺ concentration by monensin pretreatment of neurons; (2) external alkalinity, pH 8.5; (3) blockade of the mitochondrial Ca²⁺ uptake with antimycin plus oligomycin. Analysis of the data obtained led us to conclude that all the changes in [Ca²⁺]_i caused by Na⁺/NMDG replacement are mainly due to a release of endogenous Glu (reversed Glu uptake) and a subsequent Ca²⁺ influx through NMDA receptor-mediated channels.

【 授权许可】

Unknown