ArticleProceedings of the National Academy of Sciences of the United States of America2010
Imbalance of ionic conductances contributes to diverse symptoms of demyelination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 57 citations in OpenAlex.
- Repetitive after-discharges are more common in acquired demyelinating polyneuropathies.Scientific reports · 2026Article
- Chemogenetic Schwann cell activation impairs early myelination and triggers adult demyelination in the peripheral nervous system.Frontiers in cellular neuroscience · 2026Article
- Seizure and redox rescue in a model of glucose transport deficiency.PLoS computational biology · 2025Article
- KThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Article
- Modeling analysis of depolarization-assisted afterdischarge in hippocampal mossy fibers.Frontiers in neural circuits · 2024Article
- Ectopic burst induced by blockade of axonal potassium channels on the mouse hippocampal mossy fiber.Frontiers in cellular neuroscience · 2024Article
- Motor learning drives dynamic patterns of intermittent myelination on learning-activated axons.Nature neuroscience · 2022Article
- A Scientific Approach to Conscious Experience, Introspection, and Unconscious Processing: Vision and Blindsight.Brain sciences · 2022Review
- Normal Aging Induces Changes in the Brain and Neurodegeneration Progress: Review of the Structural, Biochemical, Metabolic, Cellular, and Molecular Changes.Frontiers in aging neuroscience · 2022Review
- Linking demyelination to compound action potential dispersion with a spike-diffuse-spike approach.Journal of mathematical neuroscience · 2019Article
- Voltage gated sodium channels as therapeutic targets for chronic pain.Journal of pain research · 2019Review
- A Process for Digitizing and Simulating Biologically Realistic Oligocellular Networks Demonstrated for the Neuro-Glio-Vascular Ensemble.Frontiers in neuroscience · 2018Article
- Transitions between classes of neuronal excitability and bifurcations induced by autapse.Scientific reports · 2017Article
- Dependence of Nociceptive Detection Thresholds on Physiological Parameters and Capsaicin-Induced Neuroplasticity: A Computational Study.Frontiers in computational neuroscience · 2016Article
- Physiological Dynamics in Demyelinating Diseases: Unraveling Complex Relationships through Computer Modeling.International journal of molecular sciences · 2015Review
- Cooperativity between remote sites of ectopic spiking allows afterdischarge to be initiated and maintained at different locations.Journal of computational neuroscience · 2015Article
- Myelin loss and axonal ion channel adaptations associated with gray matter neuronal hyperexcitability.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Primary paranode demyelination modulates slowly developing axonal depolarization in a model of axonal injury.Journal of computational neuroscience · 2014Article
- Focal axonal swellings and associated ultrastructural changes attenuate conduction velocity in central nervous system axons: a computer modeling study.Physiological reports · 2013Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Fast axonal conduction of action potentials in mammals relies on myelin insulation. Demyelination can cause slowed, blocked, desynchronized, or paradoxically excessive spiking that underlies the symptoms observed in demyelination diseases. The diversity and timing of such symptoms are poorly understood, often intermittent, and uncorrelated with disease progress. We modeled the effects of demyelination (and secondary remodeling) on intrinsic axonal excitability using Hodgkin-Huxley and reduced Morris-Lecar models. Simulations and analysis suggested a simple explanation for the breadth of symptoms and revealed that the ratio of sodium to leak conductance, g(Na)/g(L), acted as a four-way switch controlling excitability patterns that included spike failure, single spike transmission, afterdischarge, and spontaneous spiking. Failure occurred when this ratio fell below a threshold value. Afterdischarge occurred at g(Na)/g(L) just below the threshold for spontaneous spiking and required a slow inward current that allowed for two stable attractor states, one corresponding to quiescence and the other to repetitive spiking. A neuron prone to afterdischarge could function normally unless it was switched to its "pathological" attractor state; thus, although the underlying pathology may develop slowly by continuous changes in membrane conductances, a discontinuous change in axonal excitability can occur and lead to paroxysmal symptoms. We conclude that tonic and paroxysmal positive symptoms as well as negative symptoms may be a consequence of varying degrees of imbalance between g(Na) and g(L) after demyelination. The KCNK family of g(L) potassium channels may be an important target for new drugs to treat the symptoms of demyelination.
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