ReviewCardiovascular research2020
Heritable arrhythmia syndromes associated with abnormal cardiac sodium channel function: ionic and non-ionic mechanisms.
Review in Cardiovascular research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 75 citations in OpenAlex.
- Role of NADPH oxidase 2-derived reactive oxygen species in cardiac electrophysiological disorders.Channels (Austin, Tex.) · 2026Review
- Repurposing polyamines to prevent life-threatening arrhythmias in Short QT Syndrome type 3.Nature communications · 2026Article
- Optical mapping: pioneering the frontier of preclinical antiarrhythmic drug evaluation.iScience · 2026Review
- Connective tissue disorders and cardiac arrhythmias: genetic pathways, mechanistic bridges, and clinical implications.Frontiers in cardiovascular medicine · 2026Review
- MOG1medRxiv : the preprint server for health sciences · 2025Article
- PITX2 dosage-dependent changes in pacemaker cell state underlie sinus node dysfunction and atrial arrhythmias.Nature communications · 2025Article
- SCN5A Cardiomyopathy: from Ion Channel Dysfunction To Clinical Disease.Current cardiology reports · 2025Review
- The sodium/glucose cotransporter 2 inhibitor empagliflozin is a pharmacological chaperone of cardiac NaAmerican journal of physiology. Heart and circulatory physiology · 2025Article
- Clinical presentation and outcomes of patients with biallelicHeart rhythm O2 · 2025Article
- Voltage-Gated Sodium Channels: A Therapeutic Target in Ischemic Heart Disease.Reviews in cardiovascular medicine · 2025Review
- Heart Failure and Arrhythmias: Circadian and Epigenetic Interplay in Myocardial Electrophysiology.International journal of molecular sciences · 2025Review
- SCN5A variant type-dependent risk prediction in Brugada syndrome.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025Article
- Evolution of ion channels in cetaceans: a natural experiment in the tree of life.Scientific reports · 2024Article
- Genetic background determines the severity of age-dependent cardiac structural abnormalities and arrhythmia susceptibility in Scn5a-1798insD mice.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024Article
- Chronic Mexiletine Administration Increases Sodium Current in Non-Diseased Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Biomedicines · 2024Article
- Variable Penetrance and Expressivity of a Rare Pore Loss-of-Function Mutation (p.L889V) of Nav1.5 Channels in Three Spanish Families.International journal of molecular sciences · 2024Article
- Review
- Mechanistic insight into the functional role of human sinoatrial node conduction pathways and pacemaker compartments heterogeneity: A computer model analysis.PLoS computational biology · 2023Article
- SUMOylation of the cardiac sodium channel NaHeart rhythm · 2023Article
- 25 years of basic and translational science in EP Europace: novel insights into arrhythmia mechanisms and therapeutic strategies.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2023Review
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cardiac sodium channel NaV1.5, encoded by the SCN5A gene, is responsible for the fast upstroke of the action potential. Mutations in SCN5A may cause sodium channel dysfunction by decreasing peak sodium current, which slows conduction and facilitates reentry-based arrhythmias, and by enhancing late sodium current, which prolongs the action potential and sets the stage for early afterdepolarization and arrhythmias. Yet, some NaV1.5-related disorders, in particular structural abnormalities, cannot be directly or solely explained on the basis of defective NaV1.5 expression or biophysics. An emerging concept that may explain the large disease spectrum associated with SCN5A mutations centres around the multifunctionality of the NaV1.5 complex. In this alternative view, alterations in NaV1.5 affect processes that are independent of its canonical ion-conducting role. We here propose a novel classification of NaV1.5 (dys)function, categorized into (i) direct ionic effects of sodium influx through NaV1.5 on membrane potential and consequent action potential generation, (ii) indirect ionic effects of sodium influx on intracellular homeostasis and signalling, and (iii) non-ionic effects of NaV1.5, independent of sodium influx, through interactions with macromolecular complexes within the different microdomains of the cardiomyocyte. These indirect ionic and non-ionic processes may, acting alone or in concert, contribute significantly to arrhythmogenesis. Hence, further exploration of these multifunctional effects of NaV1.5 is essential for the development of novel preventive and therapeutic strategies.
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