ArticleAmerican journal of physiology. Heart and circulatory physiology2013
Different roles of the cardiac Na+/Ca2+-exchanger in ouabain-induced inotropy, cell signaling, and hypertrophy.
Article in American journal of physiology. Heart and circulatory physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- The mechanism of action of digoxin requires the sodium-dependent inactivation of the sodium-calcium exchanger.Science advances · 2025Article
- Factors that influence the Na/K-ATPase signaling and function.Frontiers in pharmacology · 2025Review
- Sensational site: the sodium pump ouabain-binding site and its ligands.American journal of physiology. Cell physiology · 2024Review
- Protective effects of GαNaunyn-Schmiedeberg's archives of pharmacology · 2024Article
- The vascular Na,K-ATPase: clinical implications in stroke, migraine, and hypertension.Clinical science (London, England : 1979) · 2023Review
- Nutraceutical, Dietary, and Lifestyle Options for Prevention and Treatment of Ventricular Hypertrophy and Heart Failure.International journal of molecular sciences · 2021Review
- Disturbed Presynaptic CaiScience · 2020Article
- Triple-Negative Breast Cancer Cells Exhibit Differential Sensitivity to Cardenolides fromJournal of natural products · 2020Article
- The Redox-Sensitive Na/K-ATPase Signaling in Uremic Cardiomyopathy.International journal of molecular sciences · 2020Review
- Hypertrophy of human embryonic stem cell-derived cardiomyocytes supported by positive feedback between CaPflugers Archiv : European journal of physiology · 2019Article
- Na/K-ATPase Signaling and Cardiac Pre/Postconditioning with Cardiotonic Steroids.International journal of molecular sciences · 2018Review
- Preconditioning and Postconditioning by Cardiac Glycosides in the Mouse Heart.Journal of cardiovascular pharmacology · 2018Article
- On the Many Actions of Ouabain: Pro-Cystogenic Effects in Autosomal Dominant Polycystic Kidney Disease.Molecules (Basel, Switzerland) · 2017Review
- Inferring gene and protein interactions using PubMed citations and consensus Bayesian networks.PloS one · 2017Article
- Pivotal role of α2 NaThe Journal of physiology · 2016Review
- Ischemia/reperfusion-induced alterations of enzymatic and signaling functions of the rat cardiac Na+/K+-ATPase: protection by ouabain preconditioning.Physiological reports · 2016Article
- Differential roles of caveolin-1 in ouabain-induced Na+/K+-ATPase cardiac signaling and contractility.Physiological genomics · 2016Article
- Regulation of Cardiac Remodeling by Cardiac Na(+)/K(+)-ATPase Isoforms.Frontiers in physiology · 2016Review
- Lack of Gαi2 leads to dilative cardiomyopathy and increased mortality in β1-adrenoceptor overexpressing mice.Cardiovascular research · 2015Article
- Role of phosphoinositide 3-kinase IA (PI3K-IA) activation in cardioprotection induced by ouabain preconditioning.Journal of molecular and cellular cardiology · 2015Article
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Authors and funding
7 authors at 5 institutions in 4 countries.
Funding
Abstract
Previous studies have shown that digitalis drugs, acting as specific inhibitors of cardiac Na(+)/K(+)-ATPase, not only cause positive inotropic effects, but also activate cell signaling pathways that lead to cardiac myocyte hypertrophy. A major aim of this work was to assess the role of Na(+)/Ca(2+)-exchanger, NCX1, in the above two seemingly related drug effects. Using a mouse with ventricular-specific knockout (KO) of NCX1, ouabain-induced positive inotropy that was evident in isolated wild-type (Wt) hearts was clearly reduced in KO hearts. Ouabain also increased Ca(2+) transient amplitudes in Wt myocytes, but not in KO myocytes. Ouabain-induced activations of ERK 1/2 were noted in Wt myocytes, but not in KO myocytes; however, ouabain activated PI3K1A and Akt in both Wt and KO myocytes. Protein synthesis rate, as a measure of hypertrophy, was increased by ouabain in Wt and KO myocytes; these drug effects were prevented by a PI3K inhibitor but not by a MEK/ERK inhibitor. Hypertrophy caused by ET-1, but not that induced by ouabain, was accompanied by upregulation of BNP gene in Wt and KO myocytes. The findings indicate 1) the necessity of NCX1 for positive inotropic action of ouabain; 2) the irrelevance of NCX1 and ERK 1/2 activation to ouabain-induced hypertrophy; and 3) that hypertrophy caused by ouabain through the activation of PI3K1A/Akt pathway is likely to be beneficial to the heart.
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