NBCe1 mediates the acute stimulation of astrocytic glycolysis by extracellular K +

Ivan Ruminot, Robin Gutiérrez, Gaspar Peña-Münzenmayer, Carolina Añazco, Tamara Sotelo-Hitschfeld, Rodrigo Lerchundi, María Isabel Niemeyer, Gary E. Shull, L. Felipe Barros

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128 Citas (Scopus)

Resumen

Excitatory synaptic transmission stimulates brain tissue glycolysis. This phenomenon is the signal detected in FDG-PET imaging and, through enhanced lactate production, is also thought to contribute to the fMRI signal. Using a method based on Forster resonance energy transfer in mouse astrocytes, we have recently observed that a small rise in extracellular K + can stimulate glycolysis by >300% within seconds. The K + response was blocked by ouabain, but intracellular engagement of the Na +/K + ATPase pump with Na + was ineffective, suggesting that the canonical feedback regulatory pathway involving the Na + pump and ATP depletion is only permissive and that a second mechanism is involved. Because of their predominant K + permeability and high expression of the electrogenic Na +/HCO - 3 cotransporter NBCe1, astrocytes respond to a rise in extracellular K + with plasma membrane depolarization and intracellular alkalinization. In the present article, we show that a fast glycolytic response can be elicited independently of K + by plasma membrane depolarization or by intracellular alkalinization. The glycolytic response to K + was absent in astrocytes from NBCe1 null mice (Slc4a4) and was blocked by functional or pharmacological inhibition of the NBCe1. Hippocampal neurons acquired K +-sensitive glycolysis upon heterologous NBCe1 expression. The phenomenon could also be reconstituted in HEK293 cells by coexpression of the NBCe1 and a constitutively open K + channel. We conclude that the NBCe1 is a key element in a feedforward mechanism linking excitatory synaptic transmission to fast modulation of glycolysis in astrocytes.

Idioma originalInglés
Páginas (desde-hasta)14264-14271
Número de páginas8
PublicaciónJournal of Neuroscience
Volumen31
N.º40
DOI
EstadoPublicada - 2011
Publicado de forma externa

Áreas temáticas de ASJC Scopus

  • Neurociencias General

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