1. Academic Validation
  2. Channel-mediated lactate release by K⁺-stimulated astrocytes

Channel-mediated lactate release by K⁺-stimulated astrocytes

  • J Neurosci. 2015 Mar 11;35(10):4168-78. doi: 10.1523/JNEUROSCI.5036-14.2015.
Tamara Sotelo-Hitschfeld 1 María I Niemeyer 2 Philipp Mächler 3 Iván Ruminot 2 Rodrigo Lerchundi 1 Matthias T Wyss 3 Jillian Stobart 3 Ignacio Fernández-Moncada 1 Rocío Valdebenito 2 Pamela Garrido-Gerter 1 Yasna Contreras-Baeza 1 Bernard L Schneider 4 Patrick Aebischer 4 Sylvain Lengacher 4 Alejandro San Martín 1 Juliette Le Douce 5 Gilles Bonvento 5 Pierre J Magistretti 6 Francisco V Sepúlveda 2 Bruno Weber 3 L Felipe Barros 7
Affiliations

Affiliations

  • 1 Centro de Estudios Científicos, Valdivia 5110466, Chile, Universidad Austral de Chile, Valdivia, Chile.
  • 2 Centro de Estudios Científicos, Valdivia 5110466, Chile.
  • 3 Institute of Pharmacology and Toxicology, University of Zürich, 8057 Zürich, Switzerland, Neuroscience Center Zürich, University and ETH Zürich, 8092 Zürich, Switzerland.
  • 4 Brain Mind Institute, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
  • 5 Commissariat 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, France, and.
  • 6 Brain Mind Institute, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland, Division of Biological and Environmental Sciences and Engineering, Kaust, Saudi Arabia.
  • 7 Centro de Estudios Científicos, Valdivia 5110466, Chile, fbarros@cecs.cl.
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.

Keywords

fluorescence microscopy; genetically encoded nanosensor; gliotransmission; membrane depolarization.

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