ArticleThe Journal of clinical investigation2010
Axon initial segment dysfunction in a mouse model of genetic epilepsy with febrile seizures plus.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
48 citing papers in PubMed, 89 citations in OpenAlex.
- Axon initial segment structure and function in health and disease.Physiological reviews · 2025Review
- Kinetics and functional consequences of BK channels activation by N-type CaFrontiers in cellular neuroscience · 2024Article
- Projection-Specific Heterogeneity of the Axon Initial Segment of Pyramidal Neurons in the Prelimbic Cortex.Neuroscience bulletin · 2023Article
- Carbogen-Induced Respiratory Acidosis Blocks Experimental Seizures by a Direct and Specific Inhibition of NaThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Clocking Epilepsies: A Chronomodulated Strategy-Based Therapy for Rhythmic Seizures.International journal of molecular sciences · 2023Review
- Pathology of Initial Axon Segments in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Related Disorders.International journal of molecular sciences · 2022Review
- A founder event causing a dominant childhood epilepsy survives 800 years through weak selective pressure.American journal of human genetics · 2022Article
- Augmented seizure susceptibility and hippocampal epileptogenesis in a translational mouse model of febrile status epilepticus.Epilepsia · 2021Article
- Altered hippocampal gene expression, glial cell population, and neuronal excitability in aminopeptidase P1 deficiency.Scientific reports · 2021Article
- Overlaps, gaps, and complexities of mouse models of Developmental and Epileptic Encephalopathy.Neurobiology of disease · 2021Review
- Ecm29-mediated proteasomal distribution modulates excitatory GABA responses in the developing brain.The Journal of cell biology · 2020Article
- SCN1B-linked early infantile developmental and epileptic encephalopathy.Annals of clinical and translational neurology · 2019Article
- Trafficking and Function of the Voltage-Gated Sodium Channel β2 Subunit.Biomolecules · 2019Review
- Voltage-gated sodium channel β subunits: The power outside the pore in brain development and disease.Neuropharmacology · 2018Review
- Feasibility and resolution limits of opto-magnetic imaging of neural network activity in brain slices using color centers in diamond.Scientific reports · 2018Article
- Ion Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies.Pharmacological reviews · 2018Review
- Voltage-Gated Sodium Channel β Subunits and Their Related Diseases.Handbook of experimental pharmacology · 2018Review
- Neurons with Multiple Axons Have Functional Axon Initial Segments.Neuroscience bulletin · 2017Article
- Sodium Channel β2 Subunits Prevent Action Potential Propagation Failures at Axonal Branch Points.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Synaptic ZnBritish journal of pharmacology · 2017Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Febrile seizures are a common childhood seizure disorder and a defining feature of genetic epilepsy with febrile seizures plus (GEFS+), a syndrome frequently associated with Na+ channel mutations. Here, we describe the creation of a knockin mouse heterozygous for the C121W mutation of the beta1 Na+ channel accessory subunit seen in patients with GEFS+. Heterozygous mice with increased core temperature displayed behavioral arrest and were more susceptible to thermal challenge than wild-type mice. Wild-type beta1 was most concentrated in the membrane of axon initial segments (AIS) of pyramidal neurons, while the beta1(C121W) mutant subunit was excluded from AIS membranes. In addition, AIS function, an indicator of neuronal excitability, was substantially enhanced in hippocampal pyramidal neurons of the heterozygous mouse specifically at higher temperatures. Computational modeling predicted that this enhanced excitability was caused by hyperpolarized voltage activation of AIS Na+ channels. This heat-sensitive increased neuronal excitability presumably contributed to the heightened thermal seizure susceptibility and epileptiform discharges seen in patients and mice with beta1(C121W) subunits. We therefore conclude that Na+ channel beta1 subunits modulate AIS excitability and that epilepsy can arise if this modulation is impaired.
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Registered trials
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.