Nodes of Ranvier during development and repair in the CNS

Abstract

Saltatory conduction of action potentials along myelinated axons depends on the nodes of Ranvier — small unmyelinated axonal domains where voltage-gated sodium channels are concentrated. Our knowledge of the complex molecular composition of these axonal domains continues to accumulate, although the mechanisms of nodal assembly, which have been elucidated in the PNS, remain only partially understood in the CNS. Besides the key role of the nodes in accelerating conduction, nodal variations are thought to allow the fine tuning of axonal conduction speed to meet information processing needs. In addition, through their multiple glial contacts, nodes seem to be important for neuron–glia interactions. As we highlight in this Review, the disorganization of axonal domains has been implicated in the pathophysiology of various neurological diseases. In multiple sclerosis, for example, nodal and perinodal disruption following demyelination, with subsequent changes in ion channel distribution, leads to altered axonal conduction and integrity. The nodal clusters regenerate concurrently with but also prior to remyelination, allowing the restoration of axonal conduction. In this article, we review current knowledge of the organization and function of nodes of Ranvier in the CNS. We go on to discuss dynamic changes in the nodes during demyelination and remyelination, highlighting the impact of these changes on neuronal physiology in health and disease as well as the associated therapeutic implications.

Key points

  • Nodes of Ranvier allow high-speed saltatory propagation of action potentials along myelinated fibres.

  • A range of mechanisms contribute to nodal protein clustering in the CNS.

  • The presence of multiple glial contacts at the nodal surface suggests that the CNS node might act as an axoglial hub, opening up new perspectives regarding neuroglial communication.

  • Variations in node of Ranvier length and diameter allow the fine-tuning of axonal conduction speed to meet information processing needs at the network scale.

  • Nodal domains might represent sites of axonal vulnerability in demyelinating diseases.

  • The disruption of node of Ranvier and paranodal junctions in CNS demyelinating diseases is associated with voltage-gated sodium and potassium channel redistribution, affecting action potential propagation and axonal integrity.

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Fig. 1: Nodes of Ranvier.
Fig. 2: Neuroglial interactions at the node of Ranvier.
Fig. 3: Molecular composition of the node of Ranvier.
Fig. 4: Determinants of action potential conduction velocity.
Fig. 5: Nodes of Ranvier and myelination and remyelination.

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Acknowledgements

The authors thank the ARSEP foundation, FRM (Fondation pour la Recherche Médicale), Bouvet-Labruyere Family, INSERM-DHOS, APHP (Assistance Publique des Hôpitaux de Paris), “Investissements d’avenir” ANR and NRJ foundation for their precious support related to basic and clinical research on remyelination. We thank Jean Michel Vallat for the electron micrograph of the node of Ranvier, and Rémi Ronzano, Thomas Roux and Elisa Mazuir for assistance with the figures. The authors thank Bernard Zalc for fruitful discussions and careful reading of the manuscript.

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All authors contributed equally to researching data for the article, discussions of the content, writing the article, and review and editing of the manuscript before submission.

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Correspondence to Catherine Lubetzki.

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Lubetzki, C., Sol-Foulon, N. & Desmazières, A. Nodes of Ranvier during development and repair in the CNS. Nat Rev Neurol 16, 426–439 (2020). https://doi.org/10.1038/s41582-020-0375-x

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