ArticleJournal of molecular and cellular cardiology2016
A novel NaV1.5 voltage sensor mutation associated with severe atrial and ventricular arrhythmias.
Article in Journal of molecular and cellular cardiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Variability in reported midpoints of (in)activation of cardiac INa.The Journal of general physiology · 2025Pooled it
- Clinical presentation and outcomes of patients with biallelicHeart rhythm O2 · 2025Article
- Biophysical mechanisms of myocardium sodium channelopathies.Pflugers Archiv : European journal of physiology · 2024Review
- Atrial Standstill in the Pediatric Population: A Multi-Institution Collaboration.JACC. Clinical electrophysiology · 2023Article
- Article
- Conformations of voltage-sensing domain III differentially define NaV channel closed- and open-state inactivation.The Journal of general physiology · 2021Review
- Functional Characterization of Two Novel Mutations inInternational journal of molecular sciences · 2021Article
- Identification of rare heterozygous linkage R965C-R1309H mutations in the pore-forming region of SCN5A gene associated with complex arrhythmia.Molecular genetics & genomic medicine · 2021Article
- Molecular Pathology of Sodium Channel Beta-Subunit Variants.Frontiers in pharmacology · 2021Article
- Comparing human iPSC-cardiomyocytes versus HEK293T cells unveils disease-causing effects of Brugada mutation A735V of NaScientific reports · 2019Article
- Genotype/Phenotype Relationship in a Consanguineal Family With Brugada Syndrome Harboring the R1632C Missense Variant in theFrontiers in physiology · 2019Article
- Dysfunctional Nav1.5 channels due to SCN5A mutations.Experimental biology and medicine (Maywood, N.J.) · 2018Review
- Sulfur-containing gaseous signal molecules, ion channels and cardiovascular diseases.British journal of pharmacology · 2018Review
- How to Connect Cardiac Excitation to the Atomic Interactions of Ion Channels.Biophysical journal · 2018Review
- Mechanisms of noncovalent β subunit regulation of NaThe Journal of general physiology · 2017Article
- Potential new mechanisms of pro-arrhythmia in arrhythmogenic cardiomyopathy: focus on calcium sensitive pathways.Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation · 2017Review
- HumanFrontiers in physiology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundInherited autosomal dominant mutations in cardiac sodium channels (NaV1.5) cause various arrhythmias, such as long QT syndrome and Brugada syndrome. Although dozens of mutations throughout the protein have been reported, there are few reported mutations within a voltage sensor S4 transmembrane segment and few that are homozygous. Here we report analysis of a novel lidocaine-sensitive recessive mutation, p.R1309H, in the NaV1.5 DIII/S4 voltage sensor in a patient with a complex arrhythmia syndrome. METHODS AND
resultsWe expressed the wild type or mutant NaV1.5 heterologously for analysis with the patch-clamp and voltage clamp fluorometry (VCF) techniques. p.R1309H depolarized the voltage-dependence of activation, hyperpolarized the voltage-dependence of inactivation, and slowed recovery from inactivation, thereby reducing the channel availability at physiologic membrane potentials. Additionally, p.R1309H increased the "late" Na(+) current. The location of the mutation in DIIIS4 prompted testing for a gating pore current. We observed an inward current at hyperpolarizing voltages that likely exacerbates the loss-of-function defects at resting membrane potentials. Lidocaine reduced the gating pore current.
conclusionsThe p.R1309H homozygous NaV1.5 mutation conferred both gain-of-function and loss-of-function effects on NaV1.5 channel activity. Reduction of a mutation-induced gating pore current by lidocaine suggested a therapeutic mechanism.
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