A quantitative analysis of L-glutamate-regulated Na+ dynamics in mouse cortical astrocytes: implications for cellular bioenergetics.

Détails

ID Serval
serval:BIB_F4E25E256E4D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A quantitative analysis of L-glutamate-regulated Na+ dynamics in mouse cortical astrocytes: implications for cellular bioenergetics.
Périodique
European Journal of Neuroscience
Auteur(s)
Chatton J.Y., Marquet P., Magistretti P.J.
ISSN
0953-816X
Statut éditorial
Publié
Date de publication
2000
Peer-reviewed
Oui
Volume
12
Numéro
11
Pages
3843-3853
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
The mode of Na+ entry and the dynamics of intracellular Na+ concentration ([Na+]i) changes consecutive to the application of the neurotransmitter glutamate were investigated in mouse cortical astrocytes in primary culture by video fluorescence microscopy. An elevation of [Na+]i was evoked by glutamate, whose amplitude and initial rate were concentration dependent. The glutamate-evoked Na+ increase was primarily due to Na+-glutamate cotransport, as inhibition of non-NMDA ionotropic receptors by 6-cyano-7-nitroquinoxiline-2,3-dione (CNQX) only weakly diminished the response and D-aspartate, a substrate of the glutamate transporter, produced [Na+]i elevations similar to those evoked by glutamate. Non-NMDA receptor activation could nevertheless be demonstrated by preventing receptor desensitization using cyclothiazide. Thus, in normal conditions non-NMDA receptors do not contribute significantly to the glutamate-evoked Na+ response. The rate of Na+ influx decreased during glutamate application, with kinetics that correlate well with the increase in [Na+]i and which depend on the extracellular concentration of glutamate. A tight coupling between Na+ entry and Na+/K+ ATPase activity was revealed by the massive [Na+]i increase evoked by glutamate when pump activity was inhibited by ouabain. During prolonged glutamate application, [Na+]i remains elevated at a new steady-state where Na+ influx through the transporter matches Na+ extrusion through the Na+/K+ ATPase. A mathematical model of the dynamics of [Na+]i homeostasis is presented which precisely defines the critical role of Na+ influx kinetics in the establishment of the elevated steady state and its consequences on the cellular bioenergetics. Indeed, extracellular glutamate concentrations of 10 microM already markedly increase the energetic demands of the astrocytes.
Mots-clé
6-Cyano-7-nitroquinoxaline-2,3-dione, Amino Acid Transport System X-AG, Animals, Animals, Newborn, Astrocytes, Benzothiadiazines, Biological Transport, Carrier Proteins, Cells, Cultured, Cerebral Cortex, Glutamate Plasma Membrane Transport Proteins, Glutamic Acid, Kainic Acid, Kinetics, Mice, Models, Theoretical, N-Methylaspartate, Sodium, Symporters, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Pubmed
Web of science
Création de la notice
24/01/2008 13:08
Dernière modification de la notice
20/08/2019 16:21
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