ArticleThe Journal of physiology2011
Regional genomic regulation of cardiac sodium-calcium exchanger by oestrogen.
Article in The Journal of physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 58 citations in OpenAlex.
- The mechanism of action of digoxin requires the sodium-dependent inactivation of the sodium-calcium exchanger.Science advances · 2025Article
- Cardiovascular risk of gender-affirming estrogen therapy in a transgender rat model.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Digital twin for sex-specific identification of class III antiarrhythmic drugs based on in vitro measurements, computer models, and machine learning tools.PLoS computational biology · 2025Article
- Exploring the mechanisms of sex-specific proarrhythmia in long QT syndrome through computational modeling.American journal of physiology. Heart and circulatory physiology · 2025Article
- Cardiac function is regulated by the sodium-dependent inhibition of the sodium-calcium exchanger NCX1.Nature communications · 2024Article
- Estrogenic Modulation of Ionic Channels, Pumps and Exchangers in Airway Smooth Muscle.International journal of molecular sciences · 2023Review
- Review
- Sex differences in heart: from basics to clinics.European journal of medical research · 2022Review
- Higher NaInternational journal of molecular sciences · 2022Article
- A case-control study to investigate association between serum uric acid levels and paroxysmal atrial fibrillation.Scientific reports · 2022Article
- The Effects of Different Hormones on Supraventricular and Ventricular Premature Contractions in Healthy Premenopausal Women.Medicina (Kaunas, Lithuania) · 2021Article
- Predominance of Heart Failure With Preserved Ejection Fraction in Postmenopausal Women: Intra- and Extra-Cardiomyocyte Maladaptive Alterations Scaffolded by Estrogen Deficiency.Frontiers in cell and developmental biology · 2021Review
- Transgenic Rabbit Models in Proarrhythmia Research.Frontiers in pharmacology · 2020Review
- The Role of 17β-Estradiol and Estrogen Receptors in Regulation of CaFrontiers in endocrinology · 2019Review
- Molecular pathways of oestrogen receptors and β-adrenergic receptors in cardiac cells: Recognition of their similarities, interactions and therapeutic value.Acta physiologica (Oxford, England) · 2018Review
- Genomic upregulation of cardiac Cav1.2α and NCX1 by estrogen in women.Biology of sex differences · 2017Article
- A multiscale computational modelling approach predicts mechanisms of female sex risk in the setting of arousal-induced arrhythmias.The Journal of physiology · 2017Article
- The link between abnormal calcium handling and electrical instability in acquired long QT syndrome--Does calcium precipitate arrhythmic storms?Progress in biophysics and molecular biology · 2016Review
- Synchronous systolic subcellular Ca2+-elevations underlie ventricular arrhythmia in drug-induced long QT type 2.Circulation. Arrhythmia and electrophysiology · 2015Article
- MicroRNA-23a participates in estrogen deficiency induced gap junction remodeling of rats by targeting GJA1.International journal of biological sciences · 2015Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Female rabbit hearts are more susceptible to torsade de pointes (TdP) in acquired long QT type 2 than males, in-part due to higher L-type Ca2+ current (ICa,L) at the base of the heart. In principle, higher Ca2+ influx via ICa,L should be balanced by higher efflux, perhaps mediated by parallel sex differences of sodium-calcium exchange (NCX) current (INCX). We now show that NCX1, like Cav1.2α, is greater at the base of female than male left ventricular epicardium and greater at the base than at the apex in both sexes. In voltage-clamp studies, inward (0, +20 mV, P < 0.04) and outward (-80, -60, -40, -20 mV, P < 0.01) INCX densities were significantly higher (1.5-2 fold) in female base compared to apex and male (base and apex) myocytes. Myocytes were incubated ±17β-oestradiol (E2 = 1 nm) and INCX was measured on days 0, 1, 2 and 3. Inward and outward INCX decreased over 2 days in female base myocytes becoming similar to INCX at the apex. E2 incubation (24 h) increased NCX1 (50%) and INCX (∼3-fold at 60 mV) in female base but not endocardium, apex or in male base myocytes. INCX upregulation by E2 was blunted by an oestrogen receptor (ER) antagonist (fulvestrant, 1 μm), and inhibition of transcription (actinomycin D, 5 μg ml-1) or translation (cycloheximide, 20 μg ml-1). Dofetilide (an IKr blocker) induced early afterdepolarizations (EADs) in female base myocytes cultured for 1 day if incubated with E2, but not without E2 or with E2+KB-R4973 (an INCX inhibitor), E2+fulvestrant or E2 with apex myocytes. Thus, E2 upregulates NCX1 by a genomic mechanism mediated by ERs, and de novo mRNA and protein biosynthesis, in a sex- and region-dependent manner which contributes to the enhanced propensity to EADs and TdP in female hearts.
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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.