ArticleNature communications2012
Structural modelling and mutant cycle analysis predict pharmacoresponsiveness of a Na(V)1.7 mutant channel.
Article in Nature communications, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 109 citations in OpenAlex.
- Article
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- Constitutive opening of the Kv7.2 pore activation gate causesProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Erythromelalgia caused by the missense mutation p.Arg220Pro in an alternatively spliced exon of SCN9A (NaV1.7).Human molecular genetics · 2024Article
- Clinical Challenges in Primary Erythromelalgia: a Real-Life Experience from a Single Center and a Diagnostic-Therapeutic Flow-Chart Proposal.Dermatology practical & conceptual · 2023Article
- The β3-subunit modulates the effect of venom peptides ProTx-II and OD1 on NaJournal of cellular physiology · 2023Article
- Molecular Dynamics Simulations of Ion Permeation in Human Voltage-Gated Sodium Channels.Journal of chemical theory and computation · 2023Article
- Gene therapy for chronic pain: emerging opportunities in target-rich peripheral nociceptors.Nature reviews. Neuroscience · 2023Review
- Stem cell-derived sensory neurons modelling inherited erythromelalgia: normalization of excitability.Brain : a journal of neurology · 2023Article
- Investigating genotype-phenotype relationship of extreme neuropathic pain disorders in a UK national cohort.Brain communications · 2023Article
- Computational design of peptides to target NaeLife · 2022Article
- Painful and non-painful diabetic neuropathy, diagnostic challenges and implications for future management.Brain : a journal of neurology · 2021Review
- Hydropathicity-based prediction of pain-causing NaV1.7 variants.BMC bioinformatics · 2021Article
- Erythromelalgia: A Child With V400M Mutation in theNeurology. Genetics · 2021Article
- Peripheral Voltage-Gated Cation Channels in Neuropathic Pain and Their Potential as Therapeutic Targets.Frontiers in pain research (Lausanne, Switzerland) · 2021Review
- Status of peripheral sodium channel blockers for non-addictive pain treatment.Nature reviews. Neurology · 2020Review
- Computational pipeline to probe NaV1.7 gain-of-function variants in neuropathic painful syndromes.Scientific reports · 2020Article
- Resilience to Stress and Resilience to Pain: Lessons from Molecular Neurobiology and Genetics.Trends in molecular medicine · 2020Review
- Differential effect of lacosamide on Nav1.7 variants from responsive and non-responsive patients with small fibre neuropathy.Brain : a journal of neurology · 2020Article
- An Effective Electric Dipole Model for Voltage-induced Gating Mechanism of Lysenin.Scientific reports · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Sodium channel Na(V)1.7 is critical for human pain signalling. Gain-of-function mutations produce pain syndromes including inherited erythromelalgia, which is usually resistant to pharmacotherapy, but carbamazepine normalizes activation of Na(V)1.7-V400M mutant channels from a family with carbamazepine-responsive inherited erythromelalgia. Here we show that structural modelling and thermodynamic analysis predict pharmacoresponsiveness of another mutant channel (S241T) that is located 159 amino acids distant from V400M. Structural modelling reveals that Na(v)1.7-S241T is ~2.4 Å apart from V400M in the folded channel, and thermodynamic analysis demonstrates energetic coupling of V400M and S241T during activation. Atomic proximity and energetic coupling are paralleled by pharmacological coupling, as carbamazepine (30 μM) depolarizes S214T activation, as previously reported for V400M. Pharmacoresponsiveness of S241T to carbamazepine was further evident at a cellular level, where carbamazepine normalized the hyperexcitability of dorsal root ganglion neurons expressing S241T. We suggest that this approach might identify variants that confer enhanced pharmacoresponsiveness on a variety of channels.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.