title: NBCe1 mediates the acute stimulation of astrocytic glycolysis by extracellular K+.
abstract: 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(+)/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.
authors: Centro de Estudios Científicos (CECs), Valdivia, Chile.
authors: Iván
authors: I
authors: Ruminot
authors: Robin
authors: R
authors: Gutiérrez
authors: Gaspar
authors: G
authors: Peña-Münzenmayer
authors: Carolina
authors: C
authors: Añazco
authors: Tamara
authors: T
authors: Sotelo-Hitschfeld
authors: Rodrigo
authors: R
authors: Lerchundi
authors: María Isabel
authors: MI
authors: Niemeyer
authors: Gary E
authors: GE
authors: Shull
authors: L Felipe
authors: LF
authors: Barros
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D005110:Extracellular Space / Q000378:metabolism*; D006019:Glycolysis / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D011188:Potassium / Q000378:metabolism*; D027982:Sodium-Bicarbonate Symporters / Q000502:physiology*; D013997:Time Factors
chemical_list: C498898:SLC4A4 protein, human; D027982:Sodium-Bicarbonate Symporters; D011188:Potassium