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Cellular and Molecular Life Sciences

, Volume 73, Issue 4, pp 723–735

First Online: 29 October 2015Received: 15 September 2015Revised: 21 October 2015Accepted: 22 October 2015DOI: 10.1007-s00018-015-2081-1

Cite this article as: Freeman, S.A., Desmazières, A., Fricker, D. et al. Cell. Mol. Life Sci. 2016 73: 723. doi:10.1007-s00018-015-2081-1


The efficient propagation of action potentials along nervous fibers is necessary for animals to interact with the environment with timeliness and precision. Myelination of axons is an essential step to ensure fast action potential propagation by saltatory conduction, a process that requires highly concentrated voltage-gated sodium channels at the nodes of Ranvier. Recent studies suggest that the clustering of sodium channels can influence axonal impulse conduction in both myelinated and unmyelinated fibers, which could have major implications in disease, particularly demyelinating pathology. This comprehensive review summarizes the mechanisms governing the clustering of sodium channels at the peripheral and central nervous system nodes and the specific roles of their clustering in influencing action potential conduction. We further highlight the classical biophysical parameters implicated in conduction timing, followed by a detailed discussion on how sodium channel clustering along unmyelinated axons can impact axonal impulse conduction in both physiological and pathological contexts.

KeywordsVoltage-gated sodium channel Node of ranvier Axon–glial interactions Myelin Action potential propagation Neurological disease AbbreviationsAPAction potential

AISAxon initial segment

NavVoltage-gated sodium channels

KvVoltage-gated potassium channels

PNSPeripheral nervous system

CNSCentral nervous system

CAMCell-adhesion molecule

ECMExtracellular matrix


GPIGlycosyl phosphatidylinositol

MSMultiple sclerosis

GBSGuillain–Barré syndrome

EAEExperimental autoimmune encephalomyelitis

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Autor: Sean A. Freeman - Anne Desmazières - Desdemona Fricker - Catherine Lubetzki - Nathalie Sol-Foulon


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