ArticleThe Journal of physiology2008
Paroxysmal extreme pain disorder mutations within the D3/S4-S5 linker of Nav1.7 cause moderate destabilization of fast inactivation.
Article in The Journal of physiology, 2008. 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, 92 citations in OpenAlex.
- Inherited pain: sodium channel Nav1.7 A1632T mutation causes erythromelalgia due to a shift of fast inactivation.The Journal of biological chemistry · 2014Trial
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- Nociceptor sodium channels shape subthreshold phase, upstroke, and shoulder of action potentials.The Journal of general physiology · 2025Article
- Peripheral temperature dysregulation associated with functionally altered NaPflugers Archiv : European journal of physiology · 2023Article
- Cold and warmth intensify pain-linked sodium channel gating effects and persistent currents.The Journal of general physiology · 2023Article
- Differential expression of slow and fast-repriming tetrodotoxin-sensitive sodium currents in dorsal root ganglion neurons.Frontiers in molecular neuroscience · 2023Article
- Development of automated patch clamp assays to overcome the burden of variants of uncertain significance in inheritable arrhythmia syndromes.Frontiers in physiology · 2023Review
- There is no F in APC: Using physiological fluoride-free solutions for high throughput automated patch clamp experiments.Frontiers in molecular neuroscience · 2022Article
- Ranolazine: An Old Drug with Emerging Potential; Lessons from Pre-Clinical and Clinical Investigations for Possible Repositioning.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Contributions of NaScientific reports · 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
- Block of Voltage-Gated Sodium Channels by Atomoxetine in a State- and Use-dependent Manner.Frontiers in pharmacology · 2021Article
- Computational pipeline to probe NaV1.7 gain-of-function variants in neuropathic painful syndromes.Scientific reports · 2020Article
- Paroxysmal extreme pain disorder in family with c.3892G > T (p.Val1298Phe) in the SCN9A gene mutation - case report.BMC neurology · 2020Article
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- CRMP2 and voltage-gated ion channels: potential roles in neuropathic pain.Neuronal signaling · 2018Article
- Structure-based assessment of disease-related mutations in human voltage-gated sodium channels.Protein & cell · 2017Review
- Network topology of NaV1.7 mutations in sodium channel-related painful disorders.BMC systems biology · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Single-point missense mutations in the peripheral neuronal voltage-gated sodium channel Nav1.7 are implicated in the painful inherited neuropathy paroxysmal extreme pain disorder (PEPD). The Nav1.7 PEPD mutations are located in regions of the channel suggested to play important roles in fast inactivation. PEPD mutations in the putative inactivation gate have been reported to significantly impair fast inactivation, resulting in pronounced persistent currents. However, PEPD mutations in the S4-S5 linker of domain 3 (D3/S4-S5) had not been characterized and the roles of specific residues in this linker in channel gating are unclear. We functionally characterized two of the D3/S4-S5 PEPD mutations (V1298F and V1299F) and compared their effects on gating to an adjacent non-PEPD mutation (V1300F) and the I1461T PEPD mutation, located in the putative inactivation gate. The primary effect of the V1298F and V1299F mutations is to shift the voltage dependence of fast inactivation by approximately 20 mV in the depolarizing direction. We observed a similar effect with the PEPD mutation I1461T. Interestingly, while all three PEPD mutations increased persistent currents, the relative amplitudes (approximately 6% of peak) were much smaller than previously reported for the I1461T mutation. In contrast, the main effect of the V1300F mutation was a depolarizing shift in the voltage dependence of activation. These data demonstrate that (1) mutations within D3/S4-S5 affect inactivation of Nav1.7 in a residue-specific manner and (2) disruption of the fast-inactivated state by PEPD mutations can be more moderate than previously indicated, which has important implications for the pathophysiology of PEPD.
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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.