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The sodium channel isoform transition at developing nodes of Ranvier in the peripheral nervous system: dependence on a Genetic program and myelination-induced cluster formation.

The Journal of comparative neurology | 2014

Among sodium channel isoforms, Nav 1.6 is selectively expressed at nodes of Ranvier in both the CNS and the PNS. However, non-Nav 1.6 isoforms such as Nav 1.2 are also present at the CNS nodes in early development but gradually diminish later. It has been proposed that myelination is part of a glia-neuron signaling mechanism that produces this change in nodal isoform expression. The present study used isoform-specific antibodies to demonstrate that, in the PNS, four other neuronal sodium channel isoforms were also clustered at nodes in early development but eventually disappeared during maturation. To study possible roles of myelination in such transitions, we investigated the nodal expression of selected isoforms in the sciatic nerve of the transgenic mouse Oct6(ΔSCE/βgeo) , whose PNS myelination is delayed in the first postnatal week but eventually resumes. We found that delayed myelination retarded the formation of nodal channel clusters and altered the expression-elimination patterns of sodium channel isoforms, resulting in significantly reduced expression levels of non-Nav 1.6 isoforms in such delayed nodes. However, delayed myelination did not significantly affect the gene expression, protein synthesis, or axonal trafficking of any isoform studied. Rather, we found evidence for a developmentally programmed increase in neuronal Nav 1.6 expression with constant or decreasing neuronal expression of other isoforms that were unaffected by delayed myelination. Thus our results suggest that, in the developmental isoform switch of the PNS, myelination does not play a signaling role as that proposed for the CNS but rather serves only to form nodal clusters from existing isoform pools.

Pubmed ID: 25048219 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


Antibody Registry (tool)

RRID:SCR_006397

Public registry of antibodies with unique identifiers for commercial and non-commercial antibody reagents to give researchers a way to universally identify antibodies used in publications. The registry contains antibody product information organized according to genes, species, reagent types (antibodies, recombinant proteins, ELISA, siRNA, cDNA clones). Data is provided in many formats so that authors of biological papers, text mining tools and funding agencies can quickly and accurately identify the antibody reagents they and their colleagues used. The Antibody Registry allows any user to submit a new antibody or set of antibodies to the registry via a web form, or via a spreadsheet upload.

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Nav 1.8 (antibody)

RRID:AB_2314859

This unknown targets

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Nav1.7 antibody (antibody)

RRID:AB_2315789

This polyclonal targets Nav1.7

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pan-specific sodium channel (antibody)

RRID:AB_2315782

This polyclonal targets all voltage-gated sodium channel isoform

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Nav1.6 (antibody)

RRID:AB_2314862

This unknown targets

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Ingenuity Pathway Analysis (pathway analysis tool)

RRID:SCR_008653

A web-based software application that enables users to analyze, integrate, and understand data derived from gene expression, microRNA, and SNP microarrays, metabolomics, proteomics, and RNA-Seq experiments, and small-scale experiments that generate gene and chemical lists. Users can search for targeted information on genes, proteins, chemicals, and drugs, and build interactive models of experimental systems. IPA allows exploration of molecular, chemical, gene, protein and miRNA interactions, creation of custom molecular pathways, and the ability to view and modify metabolic, signaling, and toxicological canonical pathways. In addition to the networks and pathways that can be created, IPA can provide multiple layering of additional information, such as drugs, disease genes, expression data, cellular functions and processes, or a researchers own genes or chemicals of interest.

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ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

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pan-specific sodium channel (antibody)

RRID:AB_2315782

This polyclonal targets all voltage-gated sodium channel isoform

View all literature mentions

Nav 1.8 (antibody)

RRID:AB_2314859

This unknown targets

View all literature mentions

Nav1.6 (antibody)

RRID:AB_2314862

This unknown targets

View all literature mentions

Nav 1.8 (antibody)

RRID:AB_2314859

This unknown targets

View all literature mentions

Nav1.7 antibody (antibody)

RRID:AB_2315789

This polyclonal targets Nav1.7

View all literature mentions