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Non-Canonical Control of Neuronal Energy Status by the Na+ Pump.

  • Baeza-Lehnert F Centro de Estudios Científicos (CECs), Casilla 1469, 5110466 Valdivia, Chile; Universidad Austral de Chile, Valdivia, Chile.
  • Saab AS Institute of Pharmacology and Toxicology, University and ETH Zurich, Switzerland; Neuroscience Center Zurich, Zurich, Switzerland.
  • Gutiérrez R Centro de Estudios Científicos (CECs), Casilla 1469, 5110466 Valdivia, Chile; Universidad Austral de Chile, Valdivia, Chile.
  • Larenas V Centro de Estudios Científicos (CECs), Casilla 1469, 5110466 Valdivia, Chile.
  • Díaz E Centro de Estudios Científicos (CECs), Casilla 1469, 5110466 Valdivia, Chile; Universidad Austral de Chile, Valdivia, Chile.
  • Horn M Centro de Estudios Científicos (CECs), Casilla 1469, 5110466 Valdivia, Chile.
  • Vargas M Centro de Estudios Científicos (CECs), Casilla 1469, 5110466 Valdivia, Chile; Universidad Austral de Chile, Valdivia, Chile.
  • Hösli L Institute of Pharmacology and Toxicology, University and ETH Zurich, Switzerland; Neuroscience Center Zurich, Zurich, Switzerland.
  • Stobart J Institute of Pharmacology and Toxicology, University and ETH Zurich, Switzerland; Neuroscience Center Zurich, Zurich, Switzerland.
  • Hirrlinger J Carl-Ludwig-Institute for Physiology, Faculty of Medicine, University of Leipzig, 04103 Leipzig, Germany; Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Hermann-Rein-Str. 3, 37075 Göttingen, Germany.
  • Weber B Institute of Pharmacology and Toxicology, University and ETH Zurich, Switzerland; Neuroscience Center Zurich, Zurich, Switzerland.
  • Barros LF Centro de Estudios Científicos (CECs), Casilla 1469, 5110466 Valdivia, Chile. Electronic address: fbarros@cecs.cl.
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  • 2018-12-12
Published in:
  • Cell metabolism. - 2019
ATP:ADP
ATeam 1.03
FLII12Pglu700μΔ6
Na(+)/K(+) ATPase
glucose
laconic
lactate
perceval HR
pyronic
pyruvate
Adenosine Triphosphate
Animals
Astrocytes
Energy Metabolism
Glucose
Glycolysis
Homeostasis
Mice, Inbred C57BL
Mitochondria
Neurons
Sodium-Potassium-Exchanging ATPase
English Neurons have limited intracellular energy stores but experience acute and unpredictable increases in energy demand. To better understand how these cells repeatedly transit from a resting to active state without undergoing metabolic stress, we monitored their early metabolic response to neurotransmission using ion-sensitive probes and FRET sensors in vitro and in vivo. A short theta burst triggered immediate Na+ entry, followed by a delayed stimulation of the Na+/K+ ATPase pump. Unexpectedly, cytosolic ATP and ADP levels were unperturbed across a wide range of physiological workloads, revealing strict flux coupling between the Na+ pump and mitochondria. Metabolic flux measurements revealed a "priming" phase of mitochondrial energization by pyruvate, whereas glucose consumption coincided with delayed Na+ pump stimulation. Experiments revealed that the Na+ pump plays a permissive role for mitochondrial ATP production and glycolysis. We conclude that neuronal energy homeostasis is not mediated by adenine nucleotides or by Ca2+, but by a mechanism commanded by the Na+ pump.
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  • English
Open access status
bronze
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https://sonar.ch/global/documents/185342
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