ArticlePLoS computational biology2014
Bistable dynamics underlying excitability of ion homeostasis in neuron models.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 62 citations in OpenAlex.
- The rise and deceleration of neuronal excitability in aging and Alzheimer's disease: Mechanisms, implications, and therapeutic targets.Ageing research reviews · 2026Review
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- Exosome-Based Therapeutics: A Natural Solution to Overcoming the Blood-Brain Barrier in Neurodegenerative Diseases.MedComm · 2025Review
- The Na+/K+-ATPase generically enables deterministic bursting in class I neurons by shearing the spike-onset bifurcation structure.PLoS computational biology · 2024Article
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- The Donnan-dominated resting state of skeletal muscle fibers contributes to resilience and longevity in dystrophic fibers.The Journal of general physiology · 2022Article
- An electrodiffusive neuron-extracellular-glia model for exploring the genesis of slow potentials in the brain.PLoS computational biology · 2021Article
- Activity-mediated accumulation of potassium induces a switch in firing pattern and neuronal excitability type.PLoS computational biology · 2021Article
- An electrodiffusive, ion conserving Pinsky-Rinzel model with homeostatic mechanisms.PLoS computational biology · 2020Article
- Finite Element Simulation of Ionic Electrodiffusion in Cellular Geometries.Frontiers in neuroinformatics · 2020Article
- Regulation of CSF and Brain Tissue Sodium Levels by the Blood-CSF and Blood-Brain Barriers During Migraine.Frontiers in computational neuroscience · 2020Article
- A mathematical model of recurrent spreading depolarizations.Journal of computational neuroscience · 2018Article
- The role of glutamate in neuronal ion homeostasis: A case study of spreading depolarization.PLoS computational biology · 2017Article
- A Biophysical Model for Cytotoxic Cell Swelling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Interaction between synaptic inhibition and glial-potassium dynamics leads to diverse seizure transition modes in biophysical models of human focal seizures.Journal of computational neuroscience · 2016Article
- Mechanisms of spreading depolarization in vertebrate and insect central nervous systems.Journal of neurophysiology · 2016Review
- Neuroprotective Role of Gap Junctions in a Neuron Astrocyte Network Model.Biophysical journal · 2016Article
- Large extracellular space leads to neuronal susceptibility to ischemic injury in a Na+/K+ pumps-dependent manner.Journal of computational neuroscience · 2016Article
- Near-Infrared Spectroscopy - Electroencephalography-Based Brain-State-Dependent Electrotherapy: A Computational Approach Based on Excitation-Inhibition Balance Hypothesis.Frontiers in neurology · 2016Article
- Anions Govern Cell Volume: A Case Study of Relative Astrocytic and Neuronal Swelling in Spreading Depolarization.PloS one · 2016Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
When neurons fire action potentials, dissipation of free energy is usually not directly considered, because the change in free energy is often negligible compared to the immense reservoir stored in neural transmembrane ion gradients and the long-term energy requirements are met through chemical energy, i.e., metabolism. However, these gradients can temporarily nearly vanish in neurological diseases, such as migraine and stroke, and in traumatic brain injury from concussions to severe injuries. We study biophysical neuron models based on the Hodgkin-Huxley (HH) formalism extended to include time-dependent ion concentrations inside and outside the cell and metabolic energy-driven pumps. We reveal the basic mechanism of a state of free energy-starvation (FES) with bifurcation analyses showing that ion dynamics is for a large range of pump rates bistable without contact to an ion bath. This is interpreted as a threshold reduction of a new fundamental mechanism of ionic excitability that causes a long-lasting but transient FES as observed in pathological states. We can in particular conclude that a coupling of extracellular ion concentrations to a large glial-vascular bath can take a role as an inhibitory mechanism crucial in ion homeostasis, while the Na⁺/K⁺ pumps alone are insufficient to recover from FES. Our results provide the missing link between the HH formalism and activator-inhibitor models that have been successfully used for modeling migraine phenotypes, and therefore will allow us to validate the hypothesis that migraine symptoms are explained by disturbed function in ion channel subunits, Na⁺/K⁺ pumps, and other proteins that regulate ion homeostasis.
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