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Glutamate transport decreases mitochondrial pH and modulates oxidative metabolism in astrocytes.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2011 Mar 09; Vol. 31 (10), pp. 3550-9. - Publication Year :
- 2011
-
Abstract
- During synaptic activity, the clearance of neuronally released glutamate leads to an intracellular sodium concentration increase in astrocytes that is associated with significant metabolic cost. The proximity of mitochondria at glutamate uptake sites in astrocytes raises the question of the ability of mitochondria to respond to these energy demands. We used dynamic fluorescence imaging to investigate the impact of glutamatergic transmission on mitochondria in intact astrocytes. Neuronal release of glutamate induced an intracellular acidification in astrocytes, via glutamate transporters, that spread over the mitochondrial matrix. The glutamate-induced mitochondrial matrix acidification exceeded cytosolic acidification and abrogated cytosol-to-mitochondrial matrix pH gradient. By decoupling glutamate uptake from cellular acidification, we found that glutamate induced a pH-mediated decrease in mitochondrial metabolism that surpasses the Ca(2+)-mediated stimulatory effects. These findings suggest a model in which excitatory neurotransmission dynamically regulates astrocyte energy metabolism by limiting the contribution of mitochondria to the metabolic response, thereby increasing the local oxygen availability and preventing excessive mitochondrial reactive oxygen species production.
- Subjects :
- Analysis of Variance
Animals
Biological Transport
Cells, Cultured
Cerebral Cortex metabolism
Energy Metabolism
Hydrogen-Ion Concentration
Mice
Neurons metabolism
Amino Acid Transport System X-AG metabolism
Astrocytes metabolism
Glutamic Acid metabolism
Mitochondria metabolism
Oxygen metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 31
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 21389211
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.4378-10.2011