PMID- 11069579
OWN - NLM
STAT- MEDLINE
DCOM- 20001222
LR  - 20190815
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 12
IP  - 11
DP  - 2000 Nov
TI  - A quantitative analysis of L-glutamate-regulated Na+ dynamics in mouse cortical 
      astrocytes: implications for cellular bioenergetics.
PG  - 3843-53
AB  - 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.
FAU - Chatton, J Y
AU  - Chatton JY
AD  - Institute of Physiology and Laboratory of Neurological Research, Department of 
      Neurology, University of Lausanne Medical School, Rue du Bugnon 7, CH-1005 
      Lausanne, Switzerland. jean-yves.chatton@iphysiol.unil.ch
FAU - Marquet, P
AU  - Marquet P
FAU - Magistretti, P J
AU  - Magistretti PJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Amino Acid Transport System X-AG)
RN  - 0 (Benzothiadiazines)
RN  - 0 (Carrier Proteins)
RN  - 0 (Glutamate Plasma Membrane Transport Proteins)
RN  - 0 (Symporters)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione)
RN  - 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid)
RN  - 9NEZ333N27 (Sodium)
RN  - P71U09G5BW (cyclothiazide)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - 6-Cyano-7-nitroquinoxaline-2,3-dione/*pharmacology
MH  - *Amino Acid Transport System X-AG
MH  - Animals
MH  - Animals, Newborn
MH  - Astrocytes/cytology/drug effects/*physiology
MH  - Benzothiadiazines/pharmacology
MH  - Biological Transport/drug effects
MH  - Carrier Proteins/*metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology/*physiology
MH  - Glutamate Plasma Membrane Transport Proteins
MH  - Glutamic Acid/*physiology
MH  - Kainic Acid/pharmacology
MH  - Kinetics
MH  - Mice
MH  - Models, Theoretical
MH  - N-Methylaspartate/pharmacology
MH  - Sodium/*metabolism
MH  - *Symporters
MH  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology
EDAT- 2000/11/09 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/11/09 11:00
PHST- 2000/11/09 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/09 11:00 [entrez]
AID - ejn269 [pii]
AID - 10.1046/j.1460-9568.2000.00269.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2000 Nov;12(11):3843-53. doi: 10.1046/j.1460-9568.2000.00269.x.