ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2006
Na(V)1.7 mutant A863P in erythromelalgia: effects of altered activation and steady-state inactivation on excitability of nociceptive dorsal root ganglion neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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65 citing papers in PubMed, 153 citations in OpenAlex.
- Targeting Supramolecular Active Complexes of NaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Shaping the Action Potential in Dorsal Root and Trigeminal Ganglia Neurons: Relevance to Pain Mechanisms.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- Correction of sodium channel mutations in sensory neurons reverses aberrant properties.Brain : a journal of neurology · 2025Article
- Voltage-Gated Ion Channels in Neuropathic Pain Signaling.Life (Basel, Switzerland) · 2025Review
- 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
- Schwann cell-secreted PGECell · 2024Article
- Identification and In-Silico study of non-synonymous functional SNPs in the human SCN9A gene.PloS one · 2024Article
- Molecular determinants of resurgent sodium currents mediated by Navβ4 peptide and A-type FHFs.Frontiers in molecular neuroscience · 2024Article
- Gene therapy for chronic pain: emerging opportunities in target-rich peripheral nociceptors.Nature reviews. Neuroscience · 2023Review
- A Review of the Therapeutic Targeting of SCN9A and Nav1.7 for Pain Relief in Current Human Clinical Trials.Journal of pain research · 2023Review
- Pain triangle phenomenon in possible association with SCN9A: A case report.Molecular genetics & genomic medicine · 2022Article
- E44Q mutation in NaHeliyon · 2021Article
- Hydropathicity-based prediction of pain-causing NaV1.7 variants.BMC bioinformatics · 2021Article
- Non-extensitivity and criticality of atomic hydropathicity around a voltage-gated sodium channel's pore: a modeling study.Journal of biological physics · 2021Article
- Activating Sirt1 by resveratrol suppresses Nav1.7 expression in DRG through miR-182 and alleviates neuropathic pain in rats.Channels (Austin, Tex.) · 2020Article
- Computational pipeline to probe NaV1.7 gain-of-function variants in neuropathic painful syndromes.Scientific reports · 2020Article
- Painful and painless mutations of SCN9A and SCN11A voltage-gated sodium channels.Pflugers Archiv : European journal of physiology · 2020Review
- Noncanonical Ion Channel Behaviour in Pain.International journal of molecular sciences · 2019Review
- Anomalous enhancement of resurgent NaScientific reports · 2019Article
5 more citing papers are in PubMed but not listed here.
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7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inherited erythromelalgia/erythermalgia (IEM) is a neuropathy characterized by pain and redness of the extremities that is triggered by warmth. IEM has been associated with missense mutations of the voltage-gated sodium channel Na(V)1.7, which is preferentially expressed in most nociceptive dorsal root ganglia (DRGs) and sympathetic ganglion neurons. Several mutations occur in cytoplasmic linkers of Na(V)1.7, with only two mutations in segment 4 (S4) and S6 of domain I. We report here a simplex case with an alanine 863 substitution by proline (A863P) in S5 of domain II of Na(V)1.7. The functional effect of A863P was investigated by voltage-clamp analysis in human embryonic kidney 293 cells and by current-clamp analysis to determine the effects of A863P on firing properties of small DRG neurons. Activation of mutant channels was shifted by -8 mV, whereas steady-state fast inactivation was shifted by +10 mV, compared with wild-type (WT) channels. There was a marked decrease in the rate of deactivation of mutant channels, and currents elicited by slow ramp depolarizations were 12 times larger than for WT. These results suggested that A863P could render DRG neurons hyperexcitable. We tested this hypothesis by studying properties of rat DRG neurons transfected with either A863P or WT channels. A863P depolarized resting potential of DRG neurons by +6 mV compared with WT channels, reduced the threshold for triggering single action potentials to 63% of that for WT channels, and increased firing frequency of neurons when stimulated with suprathreshold stimuli. Thus, A863P mutant channels produce hyperexcitability in DRG neurons, which contributes to the pathophysiology of IEM.
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