ArticleThe Journal of physiology2007
A Nav1.7 channel mutation associated with hereditary erythromelalgia contributes to neuronal hyperexcitability and displays reduced lidocaine sensitivity.
Article in The Journal of physiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 183 citations in OpenAlex.
- Combinatorial logic of Nav channels in nociceptor excitability: Different degrees of synergy define distinct neuronal groups.bioRxiv : the preprint server for biology · 2026Article
- Nav1.8: Intrinsic limits on the functional effect of abrogation in DRG neurons.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- 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
- Screening of candidate analgesics using a patient-derived human iPSC model of nociception identifies putative compounds for therapeutic treatment.Clinical and translational medicine · 2025Article
- Mepyramine targets mutant Nav1.7 channels to relieve pain and erythema in primary erythromelalgia patients.Frontiers in medicine · 2025Article
- Interplay of Nav1.8 and Nav1.7 channels drives neuronal hyperexcitability in neuropathic pain.The Journal of general physiology · 2024Article
- A Novel Antigen Design Strategy to Isolate Single-Domain Antibodies that Target Human Nav1.7 and Reduce Pain in Animal Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Parvalbumin expression does not account for discrete electrophysiological profiles of glutamatergic ventral pallidal subpopulations.Addiction neuroscience · 2024Article
- Multiformity of extracellular microelectrode recordings from Aδ neurons in the dorsal root ganglia: a computational modeling study.Journal of neurophysiology · 2024Article
- Molecular determinants of resurgent sodium currents mediated by Navβ4 peptide and A-type FHFs.Frontiers in molecular neuroscience · 2024Article
- The Significance of Concentration-dependent Components in Computational Models of C-Fibers.Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference · 2023Article
- Neuropathic pain: Mechanisms and therapeutic strategies.Frontiers in cell and developmental biology · 2023Review
- Differential expression of slow and fast-repriming tetrodotoxin-sensitive sodium currents in dorsal root ganglion neurons.Frontiers in molecular neuroscience · 2023Article
- Dorsal root ganglia control nociceptive input to the central nervous system.PLoS biology · 2023Article
- [Functional vascular acrosyndromes].Innere Medizin (Heidelberg, Germany) · 2022Review
- A population ofF1000Research · 2022Article
- Enhanced slow inactivation contributes to dysfunction of a recurrent SCN2A mutation associated with developmental and epileptic encephalopathy.The Journal of physiology · 2021Article
- High frequency dorsal column spinal cord stimulation for management of erythromelalgia.BMJ case reports · 2021Article
- A Narrative Review on Perioperative Pain Management Strategies in Enhanced Recovery Pathways-The Past, Present and Future.Journal of clinical medicine · 2021Review
- Hydropathicity-based prediction of pain-causing NaV1.7 variants.BMC bioinformatics · 2021Article
24 more citing papers are in PubMed but not listed here.
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5 authors at 4 institutions in 1 country.
Funding
Abstract
Mutations in the TTX-sensitive voltage-gated sodium channel subtype Nav1.7 have been implicated in the painful inherited neuropathy, hereditary erythromelalgia. Hereditary erythromelalgia can be difficult to treat and, although sodium channels are targeted by local anaesthetics such as lidocaine (lignocaine), some patients do not respond to treatment with local anaesthetics. This study examined electrophysiological differences in Nav1.7 caused by a hereditary erythromelalgia mutation (N395K) that lies within the local anaesthetic binding site of the channel. The N395K mutation produced a hyperpolarized voltage dependence of activation, slower kinetics of deactivation, and impaired steady-state slow inactivation. Computer simulations indicate that the shift in activation is the major determinant of the hyperexcitability induced by erythromelalgia mutations in sensory neurons, but that changes in slow inactivation can modulate the overall impact on excitability. This study also investigated lidocaine inhibition of the Nav1.7-N395K channel. We show that the N395K mutation attenuates the inhibitory effects of lidocaine on both resting and inactivated Nav1.7. The IC50 for lidocaine was estimated at 500 microM for inactivated wild-type Nav1.7 and 2.8 mM for inactivated Nav1.7-N395K. The N395K mutation also significantly reduced use-dependent inhibition of lidocaine on Nav1.7 current. In contrast, a different hereditary erythromelalgia mutation (F216S), not located in the local anaesthetic binding site, had no effect on lidocaine inhibition of Nav1.7 current. Our observation of reduced lidocaine inhibition on Nav1.7-N395K shows that the residue N395 is critical for lidocaine binding to Nav1.7 and suggests that the response of individuals with hereditary erythromelalgia to lidocaine treatment may be determined, at least in part, by their specific genotype.
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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.