The clustering of voltage‐gated sodium channels in various excitable membranes

Eshed-Eisenbach, Yael; Peles, Elior

doi:10.1002/dneu.22728

Cited by 18 publications

(17 citation statements)

References 82 publications

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“…Node of Ranvier assembly in the CNS is a complex process, not fully understood to date. Three main mechanisms, implicating paranodal junction, cytoskeleton and ECM, participate to node formation, but their respective role may vary depending of the neuronal subtype considered 3,92,113,114 .…”

Section: -3) Mechanisms Of Nodal Assembly and Maintenancementioning

confidence: 99%

Nodes of Ranvier during development and repair in the CNS

2020

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Saltatory conduction of action potentials along myelinated axons depends on small unmyelinated axonal domains, the nodes of Ranvier, where voltage-gated sodium channels are concentrated. Our knowledge on the complex molecular composition of these axonal domains still accumulates, whereas mechanisms of nodal assembly, established in the peripheral nervous system, remain only partially understood in the central nervous system. Apart from their key role in accelerating conduction, novel results have suggested that nodal variations allow to finely tune axonal conduction speed, to meet information processing needs. In addition, through their multiple glial contacts, nodes now appear as key actors for neuro-glial interactions. In pathology, disorganization of axonal domains is involved in the pathophysiology of various neurological diseases. In multiple sclerosis, nodal and perinodal disruption upon demyelination, with subsequent changes of ion channels distribution leads to altered axonal conduction and integrity. Nodal clusters then reform, coincident -but also prior to -remyelination, allowing restoration of axonal conduction. Here, we will review the current knowledge on nodes of Ranvier organization and function in the central nervous system; then discuss their dynamic changes during demyelination and remyelination, highlighting their impact on neuronal physiology in health and diseases and the related therapeutic perspectives. Bullet points• Nodes of Ranvier allow high-speed, saltatory propagation of action potentials along myelinated fibers • Multiple mechanisms contribute to nodal proteins clustering in the central nervous system • Multiple glial contacts at the nodal surface suggest that CNS node might act as an axoglial hub, opening new perspectives of neuro-glia communication • Variations of nodes of Ranvier length and diameter allow to finely tune axonal conduction speed, to meet information processing needs at the network scale • Nodal domains might represent sites of axonal vulnerability in demyelinating diseases • Disruption of node of Ranvier and paranodal junctions in CNS demyelinating diseases is associated with Nav and Kv channels redistribution, impacting action potential propagation and axonal integrity.

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Section: -3) Mechanisms Of Nodal Assembly and Maintenancementioning

confidence: 99%

Nodes of Ranvier during development and repair in the CNS

2020

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“…Na V 1.6 channels cluster at high-density at the AIS and nodes of Ranvier of GM and WM axons, but can be also located on the soma, dendrites, and synapses although at a lower density (Caldwell et al, 2000 ; Dumenieu et al, 2017 ; Johnson et al, 2017 ; Eshed-Eisenbach and Peles, 2020 ). The expression level of Na V 1.6 channels is low during development, but significantly increases as the nervous system matures (Boiko et al, 2001 ; Osorio et al, 2005 ; Dumenieu et al, 2017 ).…”

Section: K + Channelsmentioning

confidence: 99%

Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function?

Boscia

Elkjaer

Illés

et al. 2021

Front. Cell. Neurosci.

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Despite significant advances in our understanding of the pathophysiology of multiple sclerosis (MS), knowledge about contribution of individual ion channels to axonal impairment and remyelination failure in progressive MS remains incomplete. Ion channel families play a fundamental role in maintaining white matter (WM) integrity and in regulating WM activities in axons, interstitial neurons, glia, and vascular cells. Recently, transcriptomic studies have considerably increased insight into the gene expression changes that occur in diverse WM lesions and the gene expression fingerprint of specific WM cells associated with secondary progressive MS. Here, we review the ion channel genes encoding K+, Ca2+, Na+, and Cl− channels; ryanodine receptors; TRP channels; and others that are significantly and uniquely dysregulated in active, chronic active, inactive, remyelinating WM lesions, and normal-appearing WM of secondary progressive MS brain, based on recently published bulk and single-nuclei RNA-sequencing datasets. We discuss the current state of knowledge about the corresponding ion channels and their implication in the MS brain or in experimental models of MS. This comprehensive review suggests that the intense upregulation of voltage-gated Na+ channel genes in WM lesions with ongoing tissue damage may reflect the imbalance of Na+ homeostasis that is observed in progressive MS brain, while the upregulation of a large number of voltage-gated K+ channel genes may be linked to a protective response to limit neuronal excitability. In addition, the altered chloride homeostasis, revealed by the significant downregulation of voltage-gated Cl− channels in MS lesions, may contribute to an altered inhibitory neurotransmission and increased excitability.

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“…10 Thus, nodes of Ranvier are an attractive paradigm for the mechanism of NMJ Na + channel clustering. 11 If the mechanisms responsible for Nav1.4 channel clustering were identified and subsequently blocked, it would then be possible to experimentally test the contribution of clustered Nav1.4 to neuromuscular synapse and muscle function.…”

Section: Introductionmentioning

confidence: 99%