钠钙交换在调节神经元钙稳态中的作用需要重新评估。

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

作者信息

Storozhevykh T, Grigortsevich N, Sorokina E, Vinskaya N, Vergun O, Pinelis V, Khodorov B

机构信息

Institute of Pediatrics, Russian Academy of Medical Sciences, Moscow.

出版信息

FEBS Lett. 1998 Jul 17;431(2):215-8. doi: 10.1016/s0014-5793(98)00758-3.

DOI:10.1016/s0014-5793(98)00758-3

PMID:9708905

Abstract

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 microM) or the NMDA channel blocker memantine (25-50 microM). 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.

摘要

在培养的大鼠小脑颗粒细胞中，通过去除细胞外Na⁺（用NMDG替代）抑制质膜Na⁺/Ca²⁺交换，导致静息时细胞内Ca²⁺浓度（[Ca²⁺]i）升高，并且从谷氨酸（Glu）引起的[Ca²⁺]i负荷中恢复时，[Ca²⁺]i的恢复出现相当大的延迟。这些效应并非由通过反向Na⁺/Ca²⁺交换的Ca²⁺内流所致，因为使用NMDA受体抑制剂AP - 5（100微摩尔）或NMDA通道阻滞剂美金刚（25 - 50微摩尔）可轻易消除或预防这些效应。Na⁺/NMDG替代的效应可通过以下方式增强：（1）通过莫能菌素预处理神经元增加细胞质Na⁺浓度；（2）细胞外碱化，pH 8.5；（3）用抗霉素加寡霉素阻断线粒体Ca²⁺摄取。对所获数据的分析使我们得出结论，Na⁺/NMDG替代引起的[Ca²⁺]i的所有变化主要是由于内源性Glu的释放（反向Glu摄取）以及随后通过NMDA受体介导的通道的Ca²⁺内流。