Type
ArticleAuthors
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.

Sepulveda, F. V.
Weber, B.
Barros, L. F.
KAUST Department
Biological and Environmental Sciences and Engineering (BESE) DivisionBioscience Program
Date
2015-03-11Online Publication Date
2015-03-11Print Publication Date
2015-03-11Permanent link to this record
http://hdl.handle.net/10754/579843
Metadata
Show full item recordAbstract
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.Citation
Channel-Mediated Lactate Release by K+-Stimulated Astrocytes 2015, 35 (10):4168 Journal of NeurosciencePublisher
Society for NeuroscienceJournal
Journal of NeurosciencePubMed ID
25762664Additional Links
http://www.jneurosci.org/cgi/doi/10.1523/JNEUROSCI.5036-14.2015ae974a485f413a2113503eed53cd6c53
10.1523/JNEUROSCI.5036-14.2015
Scopus Count
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