Channel-Mediated Lactate Release by K+-Stimulated Astrocytes

Sotelo-Hitschfeld, T; Niemeyer, MI; Machler, P; Ruminot, I; Lerchundi R.; Wyss, MT; Stobart J.; Fernandez-Moncada, I; Valdebenito, R; Garrido-Gerter, P; Contreras-Baeza, Y; Schneider, BL; Aebischer, P; Lengacher, S; San Martin, A; et. al.

Keywords: fluorescence microscopy, membrane depolarization, gliotransmission, genetically encoded nanosensor


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

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Título según WOS: Channel-Mediated Lactate Release by K+-Stimulated Astrocytes
Título según SCOPUS: Channel-mediated lactate release by K+ -stimulated astrocytes
Título de la Revista: Journal of Neuroscience
Volumen: 35
Número: 10
Editorial: Society for Neuroscience
Fecha de publicación: 2015
Página de inicio: 4168
Página final: 4178
Idioma: English