ArticleMolecular pain2015
Navβ4 regulates fast resurgent sodium currents and excitability in sensory neurons.
Article in Molecular pain, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 42 citations in OpenAlex.
- Structure and function of voltage-gated sodium channel Nav1.6: Involvement in the pathological process of neural injury.Neural regeneration research · 2026Article
- Distribution of Voltage-Gated Sodium Channels and Scaffolding Proteins on Vestibular Calyx Ending Delineates the Axon Initial Segment.The Journal of comparative neurology · 2026Article
- Magnesium Ions as Modulators of Voltage-Gated and Ligand-Gated Ion Channels in Central Neurons.International journal of molecular sciences · 2025Review
- Epigenetic Control of an Auxiliary Subunit of Voltage-Gated Sodium Channels Regulates the Strength of Drug-Cue Associations and Relapse-Like Cocaine Seeking.Biological psychiatry · 2025Article
- Contusive spinal cord injury causes Nav1.8 dysfunction to upregulate small sensory neuron excitability.The Journal of physiology · 2025Article
- Resurgent current in context: Insights from the structure and function of Na and K channels.Biophysical journal · 2024Review
- The Hodgkin-Huxley-Katz Prize Lecture: A Markov model with permeation-dependent gating that accounts for resurgent current of voltage-gated Na channels.The Journal of physiology · 2023Article
- SARS-CoV-2 airway infection results in the development of somatosensory abnormalities in a hamster model.Science signaling · 2023Article
- NaeLife · 2022Article
- SARS-CoV-2 Airway Infection Results in Time-dependent Sensory Abnormalities in a Hamster Model.bioRxiv : the preprint server for biology · 2022Article
- A-type FHFs mediate resurgent currents through TTX-resistant voltage-gated sodium channels.eLife · 2022Article
- NBI-921352, a first-in-class, NaeLife · 2022Article
- Spatial transcriptomics of dorsal root ganglia identifies molecular signatures of human nociceptors.Science translational medicine · 2022Article
- Resurgent NaNature communications · 2021Article
- Review
- Resurgent Sodium Current in Neurons of the Cerebral Cortex.Frontiers in cellular neuroscience · 2021Article
- Persistent and resurgent NaJournal of neurophysiology · 2020Article
- Article
- Differential Inhibition of Human Nav1.2 Resurgent and Persistent Sodium Currents by Cannabidiol and GS967.International journal of molecular sciences · 2020Article
- Distinct functional alterations in SCN8A epilepsy mutant channels.The Journal of physiology · 2020Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundIncreased electrical activity in peripheral sensory neurons including dorsal root ganglia (DRG) and trigeminal ganglia neurons is an important mechanism underlying pain. Voltage gated sodium channels (VGSC) contribute to the excitability of sensory neurons and are essential for the upstroke of action potentials. A unique type of VGSC current, resurgent current (INaR), generates an inward current at repolarizing voltages through an alternate mechanism of inactivation referred to as open-channel block. INaRs are proposed to enable high frequency firing and increased INaRs in sensory neurons are associated with pain pathologies. While Nav1.6 has been identified as the main carrier of fast INaR, our understanding of the mechanisms that contribute to INaR generation is limited. Specifically, the open-channel blocker in sensory neurons has not been identified. Previous studies suggest Navβ4 subunit mediates INaR in central nervous system neurons. The goal of this study was to determine whether Navβ4 regulates INaR in DRG sensory neurons.
resultsOur immunocytochemistry studies show that Navβ4 expression is highly correlated with Nav1.6 expression predominantly in medium-large diameter rat DRG neurons. Navβ4 knockdown decreased endogenous fast INaR in medium-large diameter neurons as measured with whole-cell voltage clamp. Using a reduced expression system in DRG neurons, we isolated recombinant human Nav1.6 sodium currents in rat DRG neurons and found that overexpression of Navβ4 enhanced Nav1.6 INaR generation. By contrast neither overexpression of Navβ2 nor overexpression of a Navβ4-mutant, predicted to be an inactive form of Navβ4, enhanced Nav1.6 INaR generation. DRG neurons transfected with wild-type Navβ4 exhibited increased excitability with increases in both spontaneous activity and evoked activity. Thus, Navβ4 overexpression enhanced INaR and excitability, whereas knockdown or expression of mutant Navβ4 decreased INaR generation.
conclusionINaRs are associated with inherited and acquired pain disorders. However, our ability to selectively target and study this current has been hindered due to limited understanding of how it is generated in sensory neurons. This study identified Navβ4 as an important regulator of INaR and excitability in sensory neurons. As such, Navβ4 is a potential target for the manipulation of pain sensations.
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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.