ArticleThe Journal of clinical investigation2000
A revised view of cardiac sodium channel "blockade" in the long-QT syndrome.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Gene variant effects across sodium channelopathies predict function and guide precision therapy.Brain : a journal of neurology · 2022Pooled it
- Effect of enhanced recovery after surgery on older patients undergoing transvaginal pelvic floor reconstruction surgery: a randomised controlled trial.BMC medicine · 2025Trial
- Article
- The gain of function SCN1A disorder spectrum: novel epilepsy phenotypes and therapeutic implications.Brain : a journal of neurology · 2022Article
- Article
- Conformations of voltage-sensing domain III differentially define NaV channel closed- and open-state inactivation.The Journal of general physiology · 2021Review
- Deep Mutational Scan of anCirculation. Genomic and precision medicine · 2020Article
- A protocol to study ex vivo mouse working heart at human-like heart rate.Journal of molecular and cellular cardiology · 2018Article
- An Overview of Diagnosis and Management Strategies for Long QT Syndrome.The Journal of innovations in cardiac rhythm management · 2017Review
- Molecular Pathophysiology of Congenital Long QT Syndrome.Physiological reviews · 2017Review
- Fhf2 gene deletion causes temperature-sensitive cardiac conduction failure.Nature communications · 2016Article
- FGF13 modulates the gating properties of the cardiac sodium channel NaChannels (Austin, Tex.) · 2016Article
- Functional Interactions between Distinct Sodium Channel Cytoplasmic Domains through the Action of Calmodulin.The Journal of biological chemistry · 2009Article
- Differential modulation of late sodium current by protein kinase A in R1623Q mutant of LQT3.Life sciences · 2009Article
- The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome.The Journal of clinical investigation · 2008Article
- Pharmacogenetics and anti-arrhythmic drug therapy: a theoretical investigation.American journal of physiology. Heart and circulatory physiology · 2007Article
- Modulation of Na(v)1.5 by beta1-- and beta3-subunit co-expression in mammalian cells.Pflugers Archiv : European journal of physiology · 2005Article
- Interactions of local anesthetics with voltage-gated Na+ channels.The Journal of membrane biology · 2004Review
- Utility of a simplified lidocaine and potassium infusion in diagnosing long QT syndrome among patients with borderline QTc interval prolongation.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2004Article
- An antisense oligonucleotide against H1 inhibits the classical sodium current but not ICa(TTX) in rat ventricular cells.The Journal of physiology · 2003Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in SCN5A, encoding the cardiac sodium (Na) channel, are linked to a form of the congenital long-QT syndrome (LQT3) that provokes lethal ventricular arrhythmias. These autosomal dominant mutations disrupt Na channel function, inhibiting channel inactivation, thereby causing a sustained ionic current that delays cardiac repolarization. Sodium channel-blocking antiarrhythmics, such as lidocaine, potently inhibit this pathologic Na current (I(Na)) and are being evaluated in patients with LQT3. The mechanism underlying this effect is unknown, although high-affinity "block" of the open Na channel pore has been proposed. Here we report that a recently identified LQT3 mutation (R1623Q) imparts unusual lidocaine sensitivity to the Na channel that is attributable to its altered functional behavior. Studies of lidocaine on individual R1623Q single-channel openings indicate that the open-time distribution is not changed, indicating the drug does not block the open pore as proposed previously. Rather, the mutant channels have a propensity to inactivate without ever opening ("closed-state inactivation"), and lidocaine augments this gating behavior. An allosteric gating model incorporating closed-state inactivation recapitulates the effects of lidocaine on pathologic I(Na). These findings explain the unusual drug sensitivity of R1623Q and provide a general and unanticipated mechanism for understanding how Na channel-blocking agents may suppress the pathologic, sustained Na current induced by LQT3 mutations.
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.