Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons Journal Article


Author(s): Hu, Hua; Roth, Fabian C; Vandael, David H; Jonas, Peter
Article Title: Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons
Affiliation IST Austria
Abstract: Fast-spiking, parvalbumin-expressing GABAergic interneurons (PV+-BCs) express a complex machinery of rapid signaling mechanisms, including specialized voltage-gated ion channels to generate brief action potentials (APs). However, short APs are associated with overlapping Na+ and K+ fluxes and are therefore energetically expensive. How the potentially vicious combination of high AP frequency and inefficient spike generation can be reconciled with limited energy supply is presently unclear. To address this question, we performed direct recordings from the PV+-BC axon, the subcellular structure where active conductances for AP initiation and propagation are located. Surprisingly, the energy required for the AP was, on average, only ∼1.6 times the theoretical minimum. High energy efficiency emerged from the combination of fast inactivation of Na+ channels and delayed activation of Kv3-type K+ channels, which minimized ion flux overlap during APs. Thus, the complementary tuning of axonal Na+ and K+ channel gating optimizes both fast signaling properties and metabolic efficiency. Hu et al. demonstrate that action potentials in parvalbumin-expressing GABAergic interneuron axons are energetically efficient, which is highly unexpected given their brief duration. High energy efficiency emerges from the combination of fast inactivation of voltage-gated Na+ channels and delayed activation of Kv3 channels in the axon.
Keywords: inhibition; fast spiking; Modeling; Sodium channel; Action potential; axonenergy efficiency; Kv3 channel; parvalbumin-expressing GABAergic interneuron; subcellular patch clamp
Journal Title: Neuron
Volume: 98
Issue 1
ISSN: 0896-6273
Publisher: Elsevier  
Date Published: 2018-04-04
Start Page: 156
End Page: 165.e6
Copyright Statement: CC BY-NC-ND 4.0
DOI: 10.1016/j.neuron.2018.02.024
Notes: We thank Drs. Thomas Klausberger and Arnd Roth for critically reading a previous manuscript version. We also thank Florian Marr for technical assistance, Eva Kramberger for editorial support, and Drs. Michael Hines and Ted Carnevale for useful suggestions. This project has received funding from the European Research Council (ERC) under the European Union's seventh framework programme, grant agreement number 268548 (to P.J.), under the European Union's Horizon 2020 research and innovation programme, grant agreement number 692692 (to P.J.), the Fond zur Förderung der Wissenschaftlichen Forschung (P 24909-B24; Z 312-B27, Wittgenstein award to P.J.), the Norwegian Research Council, grant agreement number 250866 (to H.H.), and the European Union's seventh framework programme (FP7-PEOPLE-2013-COFUND), grant agreement number 609020 -Scientia Fellows (to H.H. and F.C.R).
Open access: yes (OA journal)