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Inhibition of Mg 2+ Extrusion Attenuates Glutamate Excitotoxicity in Cultured Rat Hippocampal Neurons.

Authors :
Shindo Y
Yamanaka R
Hotta K
Oka K
Source :
Nutrients [Nutrients] 2020 Sep 10; Vol. 12 (9). Date of Electronic Publication: 2020 Sep 10.
Publication Year :
2020

Abstract

Magnesium plays important roles in the nervous system. An increase in the Mg <superscript>2+</superscript> concentration in cerebrospinal fluid enhances neural functions, while Mg <superscript>2+</superscript> deficiency is implicated in neuronal diseases in the central nervous system. We have previously demonstrated that high concentrations of glutamate induce excitotoxicity and elicit a transient increase in the intracellular concentration of Mg <superscript>2+</superscript> due to the release of Mg <superscript>2+</superscript> from mitochondria, followed by a decrease to below steady-state levels. Since Mg <superscript>2+</superscript> deficiency is involved in neuronal diseases, this decrease presumably affects neuronal survival under excitotoxic conditions. However, the mechanism of the Mg <superscript>2+</superscript> decrease and its effect on the excitotoxicity process have not been elucidated. In this study, we demonstrated that inhibitors of Mg <superscript>2+</superscript> extrusion, quinidine and amiloride, attenuated glutamate excitotoxicity in cultured rat hippocampal neurons. A toxic concentration of glutamate induced both Mg <superscript>2+</superscript> release from mitochondria and Mg <superscript>2+</superscript> extrusion from cytosol, and both quinidine and amiloride suppressed only the extrusion. This resulted in the maintenance of a higher Mg <superscript>2+</superscript> concentration in the cytosol than under steady-state conditions during the ten-minute exposure to glutamate. These inhibitors also attenuated the glutamate-induced depression of cellular energy metabolism. Our data indicate the importance of Mg <superscript>2+</superscript> regulation in neuronal survival under excitotoxicity.

Details

Language :
English
ISSN :
2072-6643
Volume :
12
Issue :
9
Database :
MEDLINE
Journal :
Nutrients
Publication Type :
Academic Journal
Accession number :
32927908
Full Text :
https://doi.org/10.3390/nu12092768