ArticleJCI insight2021
Modulation of the effects of class Ib antiarrhythmics on cardiac NaV1.5-encoded channels by accessory NaVβ subunits.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 15 citations in OpenAlex.
- Cardiac Electrophysiologic Effects of Different Local Anesthetics in Langendorff-Perfused Rabbit Hearts.Cardiovascular toxicology · 2026Article
- Nanoscale organization in the cell membrane dynamically modulates the biophysics of voltage-gated sodium channels.Nature communications · 2026Article
- Voltage-Gated Sodium Channels: A Therapeutic Target in Ischemic Heart Disease.Reviews in cardiovascular medicine · 2025Review
- New focus on cardiac voltage-gated sodium channel β1 and β1B: Novel targets for treating and understanding arrhythmias?Heart rhythm · 2025Review
- An overview of drug-induced sodium channel blockade and changes in cardiac conduction: Implications for drug safety.Clinical and translational science · 2024Review
- Decreased ability to manage increases in reactive oxygen species may underlie susceptibility to arrhythmias in mice lackingAmerican journal of physiology. Heart and circulatory physiology · 2024Article
- The dispensability of 14-3-3 proteins for the regulation of human cardiac sodium channel Nav1.5.PloS one · 2024Article
- Biophysical properties of NaScientific reports · 2023Article
- Differential regulation of cardiac sodium channels by intracellular fibroblast growth factors.The Journal of general physiology · 2023Article
- Cardiac sodium channel complexes and arrhythmia: structural and functional roles of the β1 and β3 subunits.The Journal of physiology · 2023Article
- Neonatal Scn1b-null mice have sinoatrial node dysfunction, altered atrial structure, and atrial fibrillation.JCI insight · 2022Article
- Increased atrial effectiveness of flecainide conferred by altered biophysical properties of sodium channels.Journal of molecular and cellular cardiology · 2022Article
- Characterizing fenestration size in sodium channel subtypes and their accessibility to inhibitors.Biophysical journal · 2022Article
- Conformations of voltage-sensing domain III differentially define NaV channel closed- and open-state inactivation.The Journal of general physiology · 2021Review
- Molecular Pathology of Sodium Channel Beta-Subunit Variants.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Native myocardial voltage-gated sodium (NaV) channels function in macromolecular complexes comprising a pore-forming (α) subunit and multiple accessory proteins. Here, we investigated the impact of accessory NaVβ1 and NaVβ3 subunits on the functional effects of 2 well-known class Ib antiarrhythmics, lidocaine and ranolazine, on the predominant NaV channel α subunit, NaV1.5, expressed in the mammalian heart. We showed that both drugs stabilized the activated conformation of the voltage sensor of domain-III (DIII-VSD) in NaV1.5. In the presence of NaVβ1, the effect of lidocaine on the DIII-VSD was enhanced, whereas the effect of ranolazine was abolished. Mutating the main class Ib drug-binding site, F1760, affected but did not abolish the modulation of drug block by NaVβ1/β3. Recordings from adult mouse ventricular myocytes demonstrated that loss of Scn1b (NaVβ1) differentially affected the potencies of lidocaine and ranolazine. In vivo experiments revealed distinct ECG responses to i.p. injection of ranolazine or lidocaine in WT and Scn1b-null animals, suggesting that NaVβ1 modulated drug responses at the whole-heart level. In the human heart, we found that SCN1B transcript expression was 3 times higher in the atria than ventricles, differences that could, in combination with inherited or acquired cardiovascular disease, dramatically affect patient response to class Ib antiarrhythmic therapies.
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