ArticleCirculation research2009
Cardiac Na+ current regulation by pyridine nucleotides.
Article in Circulation research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 118 citations in OpenAlex.
- Short SCN5A Transcript Yields a NaV1.5 Fragment Influencing Cardiac Metabolism.Circulation research · 2026Article
- Cardiac Sodium Channel Regulation: A Potential New Therapeutic Target in Cardiomyopathy.Circulation research · 2026Article
- Glycerol and Glycerol-3-Phosphate: Multifaceted Metabolites in Metabolism, Cancer, and Other Diseases.Endocrine reviews · 2026Review
- Adipose tissue gene expression and longitudinal clinical phenotypes are early biomarkers of lipid-regulating drug usage.Scientific reports · 2025Article
- GPD1L as a potential biomarker associated with Treg cell infiltration and lipid metabolism in clear cell renal cell carcinoma.Journal of translational medicine · 2025Article
- Atlas of lysine propionylation of human right atrium and ALDH6A1-NADH pathway in new-onset atrial fibrillation after coronary surgery.Communications biology · 2025Article
- Nicotinamide Mononucleotide: Research Process in Cardiovascular Diseases.International journal of molecular sciences · 2024Review
- Role of Protein Kinase C in Metabolic Regulation of Coronary Endothelial Small Conductance Calcium-Activated Potassium Channels.Journal of the American Heart Association · 2024Article
- GPD1L-A306del modifies sodium current in a family carrying the dysfunctional SCN5A-G1661R mutation associated with Brugada syndrome.Pflugers Archiv : European journal of physiology · 2024Article
- NADPH Oxidases and Oxidative Stress in the Pathogenesis of Atrial Fibrillation.Antioxidants (Basel, Switzerland) · 2023Review
- Current Uncertainties and Future Challenges Regarding NAD+ Boosting Strategies.Antioxidants (Basel, Switzerland) · 2022Review
- Preventing unfolded protein response-induced ion channel dysregulation to treat arrhythmias.Trends in molecular medicine · 2022Review
- Genomic and Non-Genomic Regulatory Mechanisms of the Cardiac Sodium Channel in Cardiac Arrhythmias.International journal of molecular sciences · 2022Review
- Promising Antioxidative Effect of Berberine in Cardiovascular Diseases.Frontiers in pharmacology · 2022Review
- Inhibition of the unfolded protein response reduces arrhythmia risk after myocardial infarction.The Journal of clinical investigation · 2021Article
- Structural and Functional Characterization of a NaCirculation research · 2021Article
- Brugada Syndrome: Warning of a Systemic Condition?Frontiers in cardiovascular medicine · 2021Review
- NovelFrontiers in cardiovascular medicine · 2021Article
- Evaluating the Use of Genetics in Brugada Syndrome Risk Stratification.Frontiers in cardiovascular medicine · 2021Article
- Sudden Cardiac Death-A New Insight Into Potentially Fatal Genetic Markers.Frontiers in medicine · 2021Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
rationaleMutations in glycerol-3-phosphate dehydrogenase 1-like (GPD1-L) protein reduce cardiac Na+ current (I(Na)) and cause Brugada Syndrome (BrS). GPD1-L has >80% amino acid homology with glycerol-3-phosphate dehydrogenase, which is involved in NAD-dependent energy metabolism.
objectiveTherefore, we tested whether NAD(H) could regulate human cardiac sodium channels (Na(v)1.5). METHODS AND
resultsHEK293 cells stably expressing Na(v)1.5 and rat neonatal cardiomyocytes were used. The influence of NADH/NAD+ on arrhythmic risk was evaluated in wild-type or SCN5A(+/-) mouse heart. A280V GPD1-L caused a 2.48+/-0.17-fold increase in intracellular NADH level (P<0.001). NADH application or cotransfection with A280V GPD1-L resulted in decreased I(Na) (0.48+/-0.09 or 0.19+/-0.04 of control group, respectively; P<0.01), which was reversed by NAD+, chelerythrine, or superoxide dismutase. NAD+ antagonism of the Na+ channel downregulation by A280V GPD1-L or NADH was prevented by a protein kinase (PK)A inhibitor, PKAI(6-22). The effects of NADH and NAD+ were mimicked by a phorbol ester and forskolin, respectively. Increasing intracellular NADH was associated with an increased risk of ventricular tachycardia in wild-type mouse hearts. Extracellular application of NAD+ to SCN5A(+/-) mouse hearts ameliorated the risk of ventricular tachycardia.
conclusionsOur results show that Na(v)1.5 is regulated by pyridine nucleotides, suggesting a link between metabolism and I(Na). This effect required protein kinase C activation and was mediated by oxidative stress. NAD+ could prevent this effect by activating PKA. Mutations of GPD1-L may downregulate Na(v)1.5 by altering the oxidized to reduced NAD(H) balance.
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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.