ArticlePLoS computational biology2012
Spontaneous excitation patterns computed for axons with injury-like impairments of sodium channels and Na/K pumps.
Article in PLoS computational biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Article
- D-ꞵ-hydroxybutyrate stabilizes hippocampal CA3-CA1 circuit during acute insulin resistance.PNAS nexus · 2024Article
- Safinamide, an inhibitor of monoamine oxidase, modulates the magnitude, gating, and hysteresis of sodium ion current.BMC pharmacology & toxicology · 2024Article
- Bursting Dynamics Based on the Persistent NaeNeuro · 2023Article
- Inhibition of Voltage-Gated NaInternational journal of molecular sciences · 2023Article
- Concerted suppressive effects of carisbamate, an anti-epileptic alkyl-carbamate drug, on voltage-gated NaFrontiers in cellular neuroscience · 2023Article
- Classification of bursting patterns: A tale of two ducks.PLoS computational biology · 2022Review
- The Donnan-dominated resting state of skeletal muscle fibers contributes to resilience and longevity in dystrophic fibers.The Journal of general physiology · 2022Article
- Interactions among diameter, myelination, and the Na/K pump affect axonal resilience to high-frequency spiking.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Comodulation of h- and NaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- A Potential Mechanism of Sodium Channel Mediating the General Anesthesia Induced by Propofol.Frontiers in cellular neuroscience · 2020Article
- Propensity for Bistability of Bursting and Silence in the Leech Heart Interneuron.Frontiers in computational neuroscience · 2018Article
- Computational study on neuronal activities arising in the pre-Bötzinger complex.Cognitive neurodynamics · 2017Article
- Ionic mechanisms underlying history-dependence of conduction delay in an unmyelinated axon.eLife · 2017Article
- 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
- Electrogenic properties of the Na⁺/K⁺ ATPase control transitions between normal and pathological brain states.Journal of neurophysiology · 2015Article
- A Mathematical Model of a Midbrain Dopamine Neuron Identifies Two Slow Variables Likely Responsible for Bursts Evoked by SK Channel Antagonists and Terminated by Depolarization Block.Journal of mathematical neuroscience · 2015Article
- Stimulation-induced ectopicity and propagation windows in model damaged axons.Journal of computational neuroscience · 2014Article
- Bistable dynamics underlying excitability of ion homeostasis in neuron models.PLoS computational biology · 2014Article
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4 authors.
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Abstract
In injured neurons, "leaky" voltage-gated sodium channels (Nav) underlie dysfunctional excitability that ranges from spontaneous subthreshold oscillations (STO), to ectopic (sometimes paroxysmal) excitation, to depolarizing block. In recombinant systems, mechanical injury to Nav1.6-rich membranes causes cytoplasmic Na(+)-loading and "Nav-CLS", i.e., coupled left-(hyperpolarizing)-shift of Nav activation and availability. Metabolic injury of hippocampal neurons (epileptic discharge) results in comparable impairment: left-shifted activation and availability and hence left-shifted I(Na-window). A recent computation study revealed that CLS-based I(Na-window) left-shift dissipates ion gradients and impairs excitability. Here, via dynamical analyses, we focus on sustained excitability patterns in mildly damaged nodes, in particular with more realistic Gaussian-distributed Nav-CLS to mimic "smeared" injury intensity. Since our interest is axons that might survive injury, pumps (sine qua non for live axons) are included. In some simulations, pump efficacy and system volumes are varied. Impacts of current noise inputs are also characterized. The diverse modes of spontaneous rhythmic activity evident in these scenarios are studied using bifurcation analysis. For "mild CLS injury", a prominent feature is slow pump/leak-mediated E(Ion) oscillations. These slow oscillations yield dynamic firing thresholds that underlie complex voltage STO and bursting behaviors. Thus, Nav-CLS, a biophysically justified mode of injury, in parallel with functioning pumps, robustly engenders an emergent slow process that triggers a plethora of pathological excitability patterns. This minimalist "device" could have physiological analogs. At first nodes of Ranvier and at nociceptors, e.g., localized lipid-tuning that modulated Nav midpoints could produce Nav-CLS, as could co-expression of appropriately differing Nav isoforms.
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