ArticlePloS one2014
Disruption of myelin leads to ectopic expression of K(V)1.1 channels with abnormal conductivity of optic nerve axons in a cuprizone-induced model of demyelination.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 57 citations in OpenAlex.
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- Isolated Uhthoff phenomenon as first manifestation of multiple sclerosis: a case report.BMC neurology · 2025Article
- KThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- New High-Affinity Peptide Ligands for Kv1.2 Channel: Selective Blockers and Fluorescent Probes.Cells · 2024Article
- Snake Venom: A Promising Source of Neurotoxins Targeting Voltage-Gated Potassium Channels.Toxins · 2023Review
- Adult-onset depletion of sulfatide leads to axonal degeneration with relative myelin sparing.Glia · 2023Article
- Interactions of the Kv1.1 Channel with Peptide Pore Blockers: A Fluorescent Analysis on Mammalian Cells.Membranes · 2023Article
- Radiochemical Synthesis and Evaluation of 3-[ACS chemical neuroscience · 2022Article
- Validating visual evoked potentials as a preclinical, quantitative biomarker for remyelination efficacy.Brain : a journal of neurology · 2022Article
- Effects of Axonal Demyelination, Inflammatory Cytokines and Divalent Cation Chelators on Thalamic HCN Channels and Oscillatory Bursting.International journal of molecular sciences · 2022Article
- Refinement of axonal conduction and myelination in the mouse optic nerve indicate an extended period of postnatal developmental plasticity.Developmental neurobiology · 2022Article
- Visual Evoked Potentials to Monitor Myelin Cuprizone-Induced Functional Changes.Frontiers in neuroscience · 2022Article
- Evaluation of the potassium channel tracer [Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Radiochemical Synthesis and Evaluation in Non-Human Primates of 3-[ACS chemical neuroscience · 2021Article
- Biomedical applications of snake venom: from basic science to autoimmunity and rheumatology.Journal of translational autoimmunity · 2021Review
- Nodes of Ranvier during development and repair in the CNS.Nature reviews. Neurology · 2020Review
- Ketogenic diet ameliorates axonal defects and promotes myelination in Pelizaeus-Merzbacher disease.Acta neuropathologica · 2019Article
- Selective Axonal Expression of the Kv1 Channel Complex in Pre-myelinated GABAergic Hippocampal Neurons.Frontiers in cellular neuroscience · 2019Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular determinants of abnormal propagation of action potentials along axons and ectopic conductance in demyelinating diseases of the central nervous system, like multiple sclerosis (MS), are poorly defined. Widespread interruption of myelin occurs in several mouse models of demyelination, rendering them useful for research. Herein, considerable myelin loss is shown in the optic nerves of cuprizone-treated demyelinating mice. Immuno-fluorescence confocal analysis of the expression and distribution of voltage-activated K⁺ channels (K(V)1.1 and 1.2 α subunits) revealed their spread from typical juxta-paranodal (JXP) sites to nodes in demyelinated axons, albeit with a disproportionate increase in the level of K(V)1.1 subunit. Functionally, in contrast to monophasic compound action potentials (CAPs) recorded in controls, responses derived from optic nerves of cuprizone-treated mice displayed initial synchronous waveform followed by a dispersed component. Partial restoration of CAPs by broad spectrum (4-aminopyridine) or K(V)1.1-subunit selective (dendrotoxin K) blockers of K⁺ currents suggest enhanced K(V)1.1-mediated conductance in the demyelinated optic nerve. Biophysical profiling of K⁺ currents mediated by recombinant channels comprised of different K(V)1.1 and 1.2 stoichiometries revealed that the enrichment of K(V)1 channels K(V)1.1 subunit endows a decrease in the voltage threshold and accelerates the activation kinetics. Together with the morphometric data, these findings provide important clues to a molecular basis for temporal dispersion of CAPs and reduced excitability of demyelinated optic nerves, which could be of potential relevance to the patho-physiology of MS and related disorders.
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