RT Journal Article SR Electronic T1 NBCe1 Mediates the Acute Stimulation of Astrocytic Glycolysis by Extracellular K+ JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 14264 OP 14271 DO 10.1523/JNEUROSCI.2310-11.2011 VO 31 IS 40 A1 Ruminot, Iván A1 Gutiérrez, Robin A1 Peña-Münzenmayer, Gaspar A1 Añazco, Carolina A1 Sotelo-Hitschfeld, Tamara A1 Lerchundi, Rodrigo A1 Niemeyer, María Isabel A1 Shull, Gary E. A1 Barros, L. Felipe YR 2011 UL http://www.jneurosci.org/content/31/40/14264.abstract AB 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 Förster 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+/HCO3− 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.