ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016
Reduced Efficacy of the KCC2 Cotransporter Promotes Epileptic Oscillations in a Subiculum Network Model.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 70 citations in OpenAlex.
- Learning Dynamics in Biophysical Spiking Network Models Are Shaped by KCC2/NKCC1 Cotransporter Stoichiometry.The European journal of neuroscience · 2026Article
- Collapsing Perisomatic Inhibition Leads to Epileptic Fast-Ripple Oscillations Caused by Pseudosynchronous Firing of CA3 Pyramidal Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Epileptic seizure biophysics: the role of local voltage difference.Military Medical Research · 2025Article
- H- and m-channel overexpression promotes seizure-like events by impairing the ability of inhibitory neurons to process correlated inputs.PLoS computational biology · 2025Article
- Downmodulation of Potassium Conductances Induces Epileptic Seizures in Cortical Network Models Via Multiple Synergistic Factors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Regulation of GABAergic neurotransmission by purinergic receptors in brain physiology and disease.Purinergic signalling · 2025Review
- Circuit Reorganization of Subicular Cell-Type-Specific Interneurons in Temporal Lobe Epilepsy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Transition to seizure in focal epilepsy: From SEEG phenomenology to underlying mechanisms.Epilepsia · 2024Article
- Cell-type specific inhibitory plasticity in subicular pyramidal cells.Frontiers in cellular neuroscience · 2024Article
- Focal seizures are organized by feedback between neural activity and ion concentration changes.eLife · 2022Article
- Non-monotonic effects of GABAergic synaptic inputs on neuronal firing.PLoS computational biology · 2022Article
- Cerebral Cavernous Malformation: Immune and Inflammatory Perspectives.Frontiers in immunology · 2022Review
- Unique Actions of GABA Arising from Cytoplasmic Chloride Microdomains.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Coincident glutamatergic depolarizations enhance GABAA receptor-dependent Cl- influx in mature and suppress Cl- efflux in immature neurons.PLoS computational biology · 2021Article
- Glial Purinergic Signaling in Neurodegeneration.Frontiers in neurology · 2021Review
- When Are Depolarizing GABAergic Responses Excitatory?Frontiers in molecular neuroscience · 2021Review
- NKCC-1 mediated ClScientific reports · 2020Article
- Connecting Pathological Cellular Mechanisms to Large-Scale Seizure Structures.Trends in neurosciences · 2020Article
- Paradoxical Anticonvulsant Effect of Cefepime in the Pentylenetetrazole Model of Seizures in Rats.Pharmaceuticals (Basel, Switzerland) · 2020Article
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Pharmacoresistant epilepsy is a chronic neurological condition in which a basal brain hyperexcitability results in paroxysmal hypersynchronous neuronal discharges. Human temporal lobe epilepsy has been associated with dysfunction or loss of the potassium-chloride cotransporter KCC2 in a subset of pyramidal cells in the subiculum, a key structure generating epileptic activities. KCC2 regulates intraneuronal chloride and extracellular potassium levels by extruding both ions. Absence of effective KCC2 may alter the dynamics of chloride and potassium levels during repeated activation of GABAergic synapses due to interneuron activity. In turn, such GABAergic stress may itself affect Cl SIGNIFICANCE STATEMENT: Ion regulation in the brain is a major determinant of neural excitability. Intracellular chloride in neurons, a partial determinant of the resting potential and the inhibitory reversal potentials, is regulated together with extracellular potassium via kation chloride cotransporters. During temporal lobe epilepsy, the homeostatic regulation of intracellular chloride is impaired in pyramidal cells, yet how this dysregulation may lead to seizures has not been explored. Using a realistic neural network model describing ion mechanisms, we show that chloride homeostasis pathology provokes seizure activity analogous to recordings from epileptogenic brain tissue. We show that there is a critical percentage of pathological cells required for seizure initiation. Our model predicts that restoration of the chloride homeostasis in pyramidal cells could be a viable antiepileptic strategy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.