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State and location dependence of action potential metabolic cost in cortical pyramidal neurons

Nature Neuroscience volume 15, pages 1007–1014 (2012)Cite this article

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Abstract

Action potential generation and conduction requires large quantities of energy to restore Na+ and K+ ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na+/K+ charge overlap as a measure of action potential energy efficiency, we found that action potential initiation in the axon initial segment (AIS) and forward propagation into the axon were energetically inefficient, depending on the resting membrane potential. In contrast, action potential backpropagation into dendrites was efficient. Computer simulations predicted that, although the AIS and nodes of Ranvier had the highest metabolic cost per membrane area, action potential backpropagation into the dendrites and forward propagation into axon collaterals dominated energy consumption in cortical pyramidal neurons. Finally, we found that the high metabolic cost of action potential initiation and propagation down the axon is a trade-off between energy minimization and maximization of the conduction reliability of high-frequency action potentials.

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Figure 1: Location dependence of action potential efficiency.
Figure 2: Effect of membrane potential on Na+ and K+ flux during axonal action potentials.
Figure 3: Axonal K+ channels rapidly activate and deactivate.
Figure 4: An eight-gate axonal K+ model predicts a high channel density.
Figure 5: K+ channel inactivation regulates Na+/K+ charge separation.
Figure 6: Action potential metabolic cost is spatially heterogeneous.
Figure 7: Axonal Na+ channel inactivation is optimal for high-frequency action potentials.

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Acknowledgements

The research leading to these results has received funding from the European Research Council under the European Community's Seventh Framework Program (FP7/2007–2013)/ERC Grant agreement n° P261114 and from the Australian National Health and Medical Research Council (NHMRC) Project Grant n° 525437 to M.H.P.K. S.H. received funding from the Heisenberg Program of the German Research Foundation (HA 6386/1-1 and 2-1). The authors are grateful to Henrik Alle and Christoph Schmidt-Hieber for discussions on earlier versions of this manuscript.

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Authors and Affiliations

  1. European Neuroscience Institute Göttingen, Göttingen, Germany

    Stefan Hallermann

  2. Carl Ludwig Institute of Physiology, Medical Faculty, University of Leipzig, Leipzig, Germany

    Stefan Hallermann

  3. Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, Amsterdam, The Netherlands

    Christiaan P J de Kock

  4. Eccles Institute of Neuroscience, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia

    Greg J Stuart & Maarten H P Kole

  5. Department of Axonal Signaling, Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands

    Maarten H P Kole

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S.H. and M.H.P.K. designed and conducted the experiments and analyzed data. C.P.J.d.K. provided the in vivo reconstructions. S.H., C.P.J.d.K., G.J.S. and M.H.P.K. wrote the paper.

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Correspondence to Maarten H P Kole.

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Hallermann, S., de Kock, C., Stuart, G. et al. State and location dependence of action potential metabolic cost in cortical pyramidal neurons. Nat Neurosci 15, 1007–1014 (2012). https://doi.org/10.1038/nn.3132

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