FHF-independent conduction of action potentials along the leak-resistant cerebellar granule cell axon

Katarzyna Dover; Christopher Marra; Sergio Solinas; Marko Popovic; Sathyaa Subramaniyam; Dejan Zecevic; Egidio D'Angelo; Mitchell Goldfarb

doi:10.1038/ncomms12895

FHF-independent conduction of action potentials along the leak-resistant cerebellar granule cell axon

Nat Commun. 2016 Sep 26:7:12895. doi: 10.1038/ncomms12895.

Authors

Katarzyna Dover^{1

2}, Christopher Marra^{1

3}, Sergio Solinas⁴, Marko Popovic⁵, Sathyaa Subramaniyam⁶, Dejan Zecevic⁵, Egidio D'Angelo^{4

6}, Mitchell Goldfarb^{1

3}

Affiliations

¹ Department of Biological Sciences, Hunter College of City University, 695 Park Avenue, New York, New York 10065, USA.
² Graduate Center of City University, Molecular, Cellular and Developmental Biology Subprogram, 365 Fifth Avenue, New York, New York 10016, USA.
³ Graduate Center of City University, Neuroscience Subprogram, 365 Fifth Avenue, New York, New York 10016, USA.
⁴ Brain Connectivity Center, C. Mondino National Neurological Institute, Via Forlanini 6, Pavia 27100, Italy.
⁵ Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA.
⁶ Department of Brain and Behavioral Science, University of Pavia, Via Forlanini 6, Pavia 27100, Italy.

Abstract

Neurons in vertebrate central nervous systems initiate and conduct sodium action potentials in distinct subcellular compartments that differ architecturally and electrically. Here, we report several unanticipated passive and active properties of the cerebellar granule cell's unmyelinated axon. Whereas spike initiation at the axon initial segment relies on sodium channel (Na_v)-associated fibroblast growth factor homologous factor (FHF) proteins to delay Na_v inactivation, distal axonal Na_vs show little FHF association or FHF requirement for high-frequency transmission, velocity and waveforms of conducting action potentials. In addition, leak conductance density along the distal axon is estimated as <1% that of somatodendritic membrane. The faster inactivation rate of FHF-free Na_vs together with very low axonal leak conductance serves to minimize ionic fluxes and energetic demand during repetitive spike conduction and at rest. The absence of FHFs from Na_vs at nodes of Ranvier in the central nervous system suggests a similar mechanism of current flux minimization along myelinated axons.

Abstract

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