ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Tetrodotoxin-resistant sodium channels in sensory neurons generate slow resurgent currents that are enhanced by inflammatory mediators.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 66 citations in OpenAlex.
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- The psychoactive cannabinoid THC inhibits peripheral nociceptors by targeting NaNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Sodium Channel Inhibitors in Clinical Development for Pain Management: A Focused Review.CNS drugs · 2026Review
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- Modulation of human dorsal root ganglion neuron firing by the Nav1.8 inhibitor suzetrigine.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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- Structural basis of inhibition of human NabioRxiv : the preprint server for biology · 2024Article
- Resurgent current in context: Insights from the structure and function of Na and K channels.Biophysical journal · 2024Review
- Eugenol and lidocaine inhibit voltage-gated NaFrontiers in pharmacology · 2024Article
- Molecular determinants of resurgent sodium currents mediated by Navβ4 peptide and A-type FHFs.Frontiers in molecular neuroscience · 2024Article
- Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Differential expression of slow and fast-repriming tetrodotoxin-sensitive sodium currents in dorsal root ganglion neurons.Frontiers in molecular neuroscience · 2023Article
- Fibroblast growth factor homologous factor 2 attenuates excitability of DRG neurons.Journal of neurophysiology · 2022Article
- Passage number affects differentiation of sensory neurons from human induced pluripotent stem cells.Scientific reports · 2022Article
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8 authors at 3 institutions in 1 country.
Funding
Abstract
Resurgent sodium currents contribute to the regeneration of action potentials and enhanced neuronal excitability. Tetrodotoxin-sensitive (TTX-S) resurgent currents have been described in many different neuron populations, including cerebellar and dorsal root ganglia (DRG) neurons. In most cases, sodium channel Nav1.6 is the major contributor to these TTX-S resurgent currents. Here we report a novel TTX-resistant (TTX-R) resurgent current recorded from rat DRG neurons. The TTX-R resurgent currents are similar to classic TTX-S resurgent currents in many respects, but not all. As with TTX-S resurgent currents, they are activated by membrane repolarization, inhibited by lidocaine, and enhanced by a peptide-mimetic of the β4 sodium channel subunit intracellular domain. However, the TTX-R resurgent currents exhibit much slower kinetics, occur at more depolarized voltages, and are sensitive to the Nav1.8 blocker A803467. Moreover, coimmunoprecipitation experiments from rat DRG lysates indicate the endogenous sodium channel β4 subunits associate with Nav1.8 in DRG neurons. These results suggest that slow TTX-R resurgent currents in DRG neurons are mediated by Nav1.8 and are generated by the same mechanism underlying TTX-S resurgent currents. We also show that both TTX-S and TTX-R resurgent currents in DRG neurons are enhanced by inflammatory mediators. Furthermore, the β4 peptide increased excitability of small DRG neurons in the presence of TTX. We propose that these slow TTX-R resurgent currents contribute to the membrane excitability of nociceptive DRG neurons under normal conditions and that enhancement of both types of resurgent currents by inflammatory mediators could contribute to sensory neuronal hyperexcitability associated with inflammatory pain.
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