2. Academic Validation
  3. Non-Canonical Control of Neuronal Energy Status by the Na+ Pump

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

  • Cell Metab. 2019 Mar 5;29(3):668-680.e4. doi: 10.1016/j.cmet.2018.11.005.
Felipe Baeza-Lehnert 1,  Aiman S Saab 2,  Robin Gutiérrez 1,  Valeria Larenas 3,  Esteban Díaz 1,  Melanie Horn 3,  Miriam Vargas 1,  Ladina Hösli 2,  Jillian Stobart 2,  Johannes Hirrlinger 4,  Bruno Weber 2,  L Felipe Barros 5
Affiliations

Affiliations

  • 1 Centro de Estudios Científicos (CECs), Casilla 1469, 5110466 Valdivia, Chile; Universidad Austral de Chile, Valdivia, Chile.
  • 2 Institute of Pharmacology and Toxicology, University and ETH Zurich, Switzerland; Neuroscience Center Zurich, Zurich, Switzerland.
  • 3 Centro de Estudios Científicos (CECs), Casilla 1469, 5110466 Valdivia, Chile.
  • 4 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.
  • 5 Centro de Estudios Científicos (CECs), Casilla 1469, 5110466 Valdivia, Chile. Electronic address: fbarros@cecs.cl.
PMID: 30527744 DOI: 10.1016/j.cmet.2018.11.005
Abstract

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.

Keywords

ATP:ADP; ATeam 1.03; FLII12Pglu700μΔ6; Na(+)/K(+) ATPase; glucose; laconic; lactate; perceval HR; pyronic; pyruvate.

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