ArticlePflugers Archiv : European journal of physiology2017
FHF2 isoforms differentially regulate Nav1.6-mediated resurgent sodium currents in dorsal root ganglion neurons.
Article in Pflugers Archiv : European journal of physiology, 2017. 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, 36 citations in OpenAlex.
- Long-term inactivation mediated by different FGF-A homologues on heterologously expressed NaV1.2 currents.The Journal of general physiology · 2026Article
- Sensory neuron-expressed FGF13 controls nociceptive signaling in diabetic neuropathy models.The Journal of clinical investigation · 2025Article
- Article
- Interneuron FGF13 regulates seizure susceptibility via a sodium channel-independent mechanism.eLife · 2025Article
- Interneuron FGF13 regulates seizure susceptibility via a sodium channel-independent mechanism.bioRxiv : the preprint server for biology · 2024Article
- Molecular determinants of resurgent sodium currents mediated by Navβ4 peptide and A-type FHFs.Frontiers in molecular neuroscience · 2024Article
- Article
- 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
- Differential regulation of cardiac sodium channels by intracellular fibroblast growth factors.The Journal of general physiology · 2023Article
- Cryo-EM structure of human voltage-gated sodium channel NaProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Fibroblast growth factor 13-mediated regulation of medium spiny neuron excitability and cocaine self-administration.Frontiers in neuroscience · 2023Article
- Fibroblast growth factor homologous factor 2 attenuates excitability of DRG neurons.Journal of neurophysiology · 2022Article
- A-type FHFs mediate resurgent currents through TTX-resistant voltage-gated sodium channels.eLife · 2022Article
- Review
- Differential Modulation of the Voltage-Gated NaFrontiers in molecular biosciences · 2021Article
- Effects of Deltamethrin Acute Exposure on Nav1.6 Channels and Medium Spiny Neurons of the Nucleus Accumbens.Toxicology · 2020Article
- FHF1 is a bona fide fibroblast growth factor that activates cellular signaling in FGFR-dependent manner.Cell communication and signaling : CCS · 2020Article
- Hemokinin-1 Gene Expression Is Upregulated in Trigeminal Ganglia in an Inflammatory Orofacial Pain Model: Potential Role in Peripheral Sensitization.International journal of molecular sciences · 2020Article
- Distinct functional alterations in SCN8A epilepsy mutant channels.The Journal of physiology · 2020Article
- Effects of FGF14 and NaThe Journal of general physiology · 2019Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Nav1.6 and Nav1.6-mediated resurgent currents have been implicated in several pain pathologies. However, our knowledge of how fast resurgent currents are modulated in neurons is limited. Our study explored the potential regulation of Nav1.6-mediated resurgent currents by isoforms of fibroblast growth factor homologous factor 2 (FHF2) in an effort to address the gap in our knowledge. FHF2 isoforms colocalize with Nav1.6 in peripheral sensory neurons. Cell line studies suggest that these proteins differentially regulate inactivation. In particular, FHF2A mediates long-term inactivation, a mechanism proposed to compete with the open-channel blocker mechanism that mediates resurgent currents. On the other hand, FHF2B lacks the ability to mediate long-term inactivation and may delay inactivation favoring open-channel block. Based on these observations, we hypothesized that FHF2A limits resurgent currents, whereas FHF2B enhances resurgent currents. Overall, our results suggest that FHF2A negatively regulates fast resurgent current by enhancing long-term inactivation and delaying recovery. In contrast, FHF2B positively regulated resurgent current and did not alter long-term inactivation. Chimeric constructs of FHF2A and Navβ4 (likely the endogenous open channel blocker in sensory neurons) exhibited differential effects on resurgent currents, suggesting that specific regions within FHF2A and Navβ4 have important regulatory functions. Our data also indicate that FHFAs and FHF2B isoform expression are differentially regulated in a radicular pain model and that associated neuronal hyperexcitability is substantially attenuated by a FHFA peptide. As such, these findings suggest that FHF2A and FHF2B regulate resurgent current in sensory neurons and may contribute to hyperexcitability associated with some pain pathologies.
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