TY - JOUR
T1 - NBCe1 mediates the acute stimulation of astrocytic glycolysis by extracellular K +
AU - Ruminot, Ivan
AU - Gutiérrez, Robin
AU - Peña-Münzenmayer, Gaspar
AU - Añazco, Carolina
AU - Sotelo-Hitschfeld, Tamara
AU - Lerchundi, Rodrigo
AU - Niemeyer, María Isabel
AU - Shull, Gary E.
AU - Barros, L. Felipe
PY - 2011/10/5
Y1 - 2011/10/5
N2 - 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.
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 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.
UR - http://www.scopus.com/inward/record.url?scp=80053635398&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.2310-11.2011
DO - 10.1523/JNEUROSCI.2310-11.2011
M3 - Article
C2 - 21976511
AN - SCOPUS:80053635398
SN - 0270-6474
VL - 31
SP - 14264
EP - 14271
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 40
ER -