ArticleAmerican journal of physiology. Heart and circulatory physiology2012
Constitutive overexpression of phosphomimetic phospholemman S68E mutant results in arrhythmias, early mortality, and heart failure: potential involvement of Na+/Ca2+ exchanger.
Article in American journal of physiology. Heart and circulatory physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 31 citations in OpenAlex.
- Desmosomal Junctions and Connexin-43 Remodeling in High-Pacing-Induced Heart Failure Dogs.Anatolian journal of cardiology · 2023Article
- Effect of C reactive protein on the sodium-calcium exchanger 1 in cardiomyocytes.Experimental and therapeutic medicine · 2021Article
- Integrated Quantitative Phosphoproteomics and Cell-based Functional Screening Reveals Specific Pathological Cardiac Hypertrophy-related Phosphorylation Sites.Molecules and cells · 2021Article
- Novel BAG3 Variants in African American Patients With Cardiomyopathy: Reduced β-Adrenergic Responsiveness in Excitation-Contraction.Journal of cardiac failure · 2020Article
- Antidotal effects of methylene blue against cyanide neurological toxicity: in vivo and in vitro studies.Annals of the New York Academy of Sciences · 2020Article
- Trpm2 enhances physiological bioenergetics and protects against pathological oxidative cardiac injury: Role of Pyk2 phosphorylation.Journal of cellular physiology · 2019Article
- Methylene Blue Counteracts HCardiovascular toxicology · 2018Article
- Haplo-insufficiency of Bcl2-associated athanogene 3 in mice results in progressive left ventricular dysfunction, β-adrenergic insensitivity, and increased apoptosis.Journal of cellular physiology · 2018Article
- Methylene blue counteracts cyanide cardiotoxicity: cellular mechanisms.Journal of applied physiology (Bethesda, Md. : 1985) · 2018Article
- Adeno-associated Virus Serotype 9 - Driven Expression of BAG3 Improves Left Ventricular Function in Murine Hearts with Left Ventricular Dysfunction Secondary to a Myocardial Infarction.JACC. Basic to translational science · 2016Article
- Development of a high-affinity peptide that prevents phospholemman (PLM) inhibition of the sodium/calcium exchanger 1 (NCX1).The Biochemical journal · 2016Article
- Methylene blue counteracts H2S toxicity-induced cardiac depression by restoring L-type Ca channel activity.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Article
- BAG3 regulates contractility and Ca(2+) homeostasis in adult mouse ventricular myocytes.Journal of molecular and cellular cardiology · 2016Article
- Cardiac Dysfunction in HIV-1 Transgenic Mouse: Role of Stress and BAG3.Clinical and translational science · 2015Article
- Regulation of L-type calcium channel by phospholemman in cardiac myocytes.Journal of molecular and cellular cardiology · 2015Article
- Ca²⁺ entry via Trpm2 is essential for cardiac myocyte bioenergetics maintenance.American journal of physiology. Heart and circulatory physiology · 2015Article
- A new cell-penetrating peptide that blocks the autoinhibitory XIP domain of NCX1 and enhances antiporter activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Targeting cardiomyocyte Ca2+ homeostasis in heart failure.Current pharmaceutical design · 2015Review
- Induced overexpression of phospholemman S68E mutant improves cardiac contractility and mortality after ischemia-reperfusion.American journal of physiology. Heart and circulatory physiology · 2014Article
- TRPM2 channels protect against cardiac ischemia-reperfusion injury: role of mitochondria.The Journal of biological chemistry · 2014Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Expression and activity of cardiac Na(+)/Ca(2+) exchanger (NCX1) are altered in many disease states. We engineered mice in which the phosphomimetic phospholemman S68E mutant (inhibits NCX1 but not Na(+)-K(+)-ATPase) was constitutively overexpressed in a cardiac-specific manner (conS68E). At 4-6 wk, conS68E mice exhibited severe bradycardia, ventricular arrhythmias, increased left ventricular (LV) mass, decreased cardiac output (CO), and ∼50% mortality compared with wild-type (WT) littermates. Protein levels of NCX1, calsequestrin, ryanodine receptor, and α(1)- and α(2)-subunits of Na(+)-K(+)-ATPase were similar, but sarco(endo)plasmic reticulum Ca(2+)-ATPase was lower, whereas L-type Ca(2+) channels were higher in conS68E hearts. Resting membrane potential and action potential amplitude were similar, but action potential duration was dramatically prolonged in conS68E myocytes. Diastolic intracellular Ca(2+) ([Ca(2+)](i)) was higher, [Ca(2+)](i) transient and maximal contraction amplitudes were lower, and half-time of [Ca(2+)](i) transient decline was longer in conS68E myocytes. Intracellular Na(+) reached maximum within 3 min after isoproterenol addition, followed by decline in WT but not in conS68E myocytes. Na(+)/Ca(2+) exchange, L-type Ca(2+), Na(+)-K(+)-ATPase, and depolarization-activated K(+) currents were decreased in conS68E myocytes. At 22 wk, bradycardia and increased LV mass persisted in conS68E survivors. Despite comparable baseline CO, conS68E survivors at 22 wk exhibited decreased chronotropic, inotropic, and lusitropic responses to isoproterenol. We conclude that constitutive overexpression of S68E mutant was detrimental, both in terms of depressed cardiac function and increased arrhythmogenesis.
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