Channel-Mediated Lactate Release by K+-Stimulated Astrocytes

Handle URI:
http://hdl.handle.net/10754/579843
Title:
Channel-Mediated Lactate Release by K+-Stimulated Astrocytes
Authors:
Sotelo-Hitschfeld, T.; Niemeyer, M. I.; Machler, P.; Ruminot, I.; Lerchundi, R.; Wyss, M. T.; Stobart, J.; Fernandez-Moncada, I.; Valdebenito, R.; Garrido-Gerter, P.; Contreras-Baeza, Y.; Schneider, B. L.; Aebischer, P.; Lengacher, S.; San Martin, A.; Le Douce, J.; Bonvento, G.; Magistretti, Pierre J. ( 0000-0002-6678-320X ) ; Sepulveda, F. V.; Weber, B.; Barros, L. F.
Abstract:
Excitatory synaptic transmission is accompanied by a local surge in interstitial lactate that occurs despite adequate oxygen availability, a puzzling phenomenon termed aerobic glycolysis. In addition to its role as an energy substrate, recent studies have shown that lactate modulates neuronal excitability acting through various targets, including NMDA receptors and G-protein-coupled receptors specific for lactate, but little is known about the cellular and molecular mechanisms responsible for the increase in interstitial lactate. Using a panel of genetically encoded fluorescence nanosensors for energy metabolites, we show here that mouse astrocytes in culture, in cortical slices, and in vivo maintain a steady-state reservoir of lactate. The reservoir was released to the extracellular space immediately after exposure of astrocytes to a physiological rise in extracellular K+ or cell depolarization. Cell-attached patch-clamp analysis of cultured astrocytes revealed a 37 pS lactate-permeable ion channel activated by cell depolarization. The channel was modulated by lactate itself, resulting in a positive feedback loop for lactate release. A rapid fall in intracellular lactate levels was also observed in cortical astrocytes of anesthetized mice in response to local field stimulation. The existence of an astrocytic lactate reservoir and its quick mobilization via an ion channel in response to a neuronal cue provides fresh support to lactate roles in neuronal fueling and in gliotransmission.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
Channel-Mediated Lactate Release by K+-Stimulated Astrocytes 2015, 35 (10):4168 Journal of Neuroscience
Publisher:
Society for Neuroscience
Journal:
Journal of Neuroscience
Issue Date:
11-Mar-2015
DOI:
10.1523/JNEUROSCI.5036-14.2015
Type:
Article
ISSN:
0270-6474; 1529-2401
Additional Links:
http://www.jneurosci.org/cgi/doi/10.1523/JNEUROSCI.5036-14.2015
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorSotelo-Hitschfeld, T.en
dc.contributor.authorNiemeyer, M. I.en
dc.contributor.authorMachler, P.en
dc.contributor.authorRuminot, I.en
dc.contributor.authorLerchundi, R.en
dc.contributor.authorWyss, M. T.en
dc.contributor.authorStobart, J.en
dc.contributor.authorFernandez-Moncada, I.en
dc.contributor.authorValdebenito, R.en
dc.contributor.authorGarrido-Gerter, P.en
dc.contributor.authorContreras-Baeza, Y.en
dc.contributor.authorSchneider, B. L.en
dc.contributor.authorAebischer, P.en
dc.contributor.authorLengacher, S.en
dc.contributor.authorSan Martin, A.en
dc.contributor.authorLe Douce, J.en
dc.contributor.authorBonvento, G.en
dc.contributor.authorMagistretti, Pierre J.en
dc.contributor.authorSepulveda, F. V.en
dc.contributor.authorWeber, B.en
dc.contributor.authorBarros, L. F.en
dc.date.accessioned2015-10-18T14:42:32Zen
dc.date.available2015-10-18T14:42:32Zen
dc.date.issued2015-03-11en
dc.identifier.citationChannel-Mediated Lactate Release by K+-Stimulated Astrocytes 2015, 35 (10):4168 Journal of Neuroscienceen
dc.identifier.issn0270-6474en
dc.identifier.issn1529-2401en
dc.identifier.doi10.1523/JNEUROSCI.5036-14.2015en
dc.identifier.urihttp://hdl.handle.net/10754/579843en
dc.description.abstractExcitatory synaptic transmission is accompanied by a local surge in interstitial lactate that occurs despite adequate oxygen availability, a puzzling phenomenon termed aerobic glycolysis. In addition to its role as an energy substrate, recent studies have shown that lactate modulates neuronal excitability acting through various targets, including NMDA receptors and G-protein-coupled receptors specific for lactate, but little is known about the cellular and molecular mechanisms responsible for the increase in interstitial lactate. Using a panel of genetically encoded fluorescence nanosensors for energy metabolites, we show here that mouse astrocytes in culture, in cortical slices, and in vivo maintain a steady-state reservoir of lactate. The reservoir was released to the extracellular space immediately after exposure of astrocytes to a physiological rise in extracellular K+ or cell depolarization. Cell-attached patch-clamp analysis of cultured astrocytes revealed a 37 pS lactate-permeable ion channel activated by cell depolarization. The channel was modulated by lactate itself, resulting in a positive feedback loop for lactate release. A rapid fall in intracellular lactate levels was also observed in cortical astrocytes of anesthetized mice in response to local field stimulation. The existence of an astrocytic lactate reservoir and its quick mobilization via an ion channel in response to a neuronal cue provides fresh support to lactate roles in neuronal fueling and in gliotransmission.en
dc.language.isoenen
dc.publisherSociety for Neuroscienceen
dc.relation.urlhttp://www.jneurosci.org/cgi/doi/10.1523/JNEUROSCI.5036-14.2015en
dc.rightsArchived with thanks to Journal of Neuroscienceen
dc.titleChannel-Mediated Lactate Release by K+-Stimulated Astrocytesen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalJournal of Neuroscienceen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionCentro de Estudios Científicos, Valdivia 5110466, Chileen
dc.contributor.institutionInstitute of Pharmacology and Toxicology, University of Zürich, 8057 Zürich, Switzerlanden
dc.contributor.institutionNeuroscience Center Zürich, University and ETH Zürich, 8092 Zürich, Switzerlanden
dc.contributor.institutionUniversidad Austral de Chile, Valdivia, Chileen
dc.contributor.institutionBrain Mind Institute, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerlanden
dc.contributor.institutionCommissariat à l'Energie Atomique, Institut d'Imagerie Biomédicale, Molecular Imaging Research Center and Centre National de la Recherche Scientifique, Université Paris-Sud, Université Paris-Saclay, UMR 9199, F-92265 Fontenay-aux-Roses, Franceen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorMagistretti, Pierre J.en
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