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