ArticleJournal of the American Heart Association2014
Interventricular differences in β-adrenergic responses in the canine heart: role of phosphodiesterases.
Article in Journal of the American Heart Association, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Ventricular arrhythmogenesis in pulmonary hypertension: From right ventricular remodeling to clinical implications.Physiological reports · 2026Review
- Review
- Review
- Phosphodiesterase 8 governs cAMP/PKA-dependent reduction of L-type calcium current in human atrial fibrillation: a novel arrhythmogenic mechanism.European heart journal · 2023Article
- Lower troponin expression in the right ventricle of rats explains interventricular differences in E-C coupling.The Journal of general physiology · 2022Article
- Asymmetry and Heterogeneity: Part and Parcel in Cardiac Autonomic Innervation and Function.Frontiers in physiology · 2021Review
- Heart Failure in Humans Reduces Contractile Force in Myocardium From Both Ventricles.JACC. Basic to translational science · 2020Article
- Mending a broken heart: current strategies and limitations of cell-based therapy.Stem cell research & therapy · 2020Review
- "Heart Oddity": Intrinsically Reduced Excitability in the Right Ventricle Requires Compensation by Regionally Specific Stress Kinase Function.Frontiers in physiology · 2020Review
- Approaches to High-Throughput Analysis of Cardiomyocyte Contractility.Frontiers in physiology · 2020Article
- Conduction in the right and left ventricle is differentially regulated by protein kinases and phosphatases: implications for arrhythmogenesis.American journal of physiology. Heart and circulatory physiology · 2019Article
- Rolipram, a PDE4 Inhibitor, Enhances the Inotropic Effect of Rat Heart by Activating SERCA2a.Frontiers in pharmacology · 2019Article
- Prolonged Intensive Exercise: When the Right Ventricle Goes Wrong.Korean circulation journal · 2018Article
- Article
- β-Adrenergic receptor stimulation inhibits proarrhythmic alternans in postinfarction border zone cardiomyocytes: a computational analysis.American journal of physiology. Heart and circulatory physiology · 2017Article
- Article
- Effects of zacopride, a moderate IPharmacological research · 2017Article
- Differences in Left Versus Right Ventricular Electrophysiological Properties in Cardiac Dysfunction and Arrhythmogenesis.Arrhythmia & electrophysiology review · 2016Article
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRV and LV have different embryologic, structural, metabolic, and electrophysiologic characteristics, but whether interventricular differences exist in β-adrenergic (β-AR) responsiveness is unknown. In this study, we examine whether β-AR response and signaling differ in right (RV) versus left (LV) ventricles. METHODS AND
resultsSarcomere shortening, Ca(2+) transients, ICa,L and IKs currents were recorded in isolated dog LV and RV midmyocytes. Intracellular [cAMP] and PKA activity were measured by live cell imaging using FRET-based sensors. Isoproterenol increased sarcomere shortening ≈10-fold and Ca(2+)-transient amplitude ≈2-fold in LV midmyocytes (LVMs) versus ≈25-fold and ≈3-fold in RVMs. FRET imaging using targeted Epac2camps sensors revealed no change in subsarcolemmal [cAMP], but a 2-fold higher β-AR stimulation of cytoplasmic [cAMP] in RVMs versus LVMs. Accordingly, β-AR regulation of ICa,L and IKs were similar between LVMs and RVMs, whereas cytoplasmic PKA activity was increased in RVMs. Both PDE3 and PDE4 contributed to the β-AR regulation of cytoplasmic [cAMP], and the difference between LVMs and RVMs was abolished by PDE3 inhibition and attenuated by PDE4 inhibition. Finally LV and RV intracavitary pressures were recorded in anesthetized beagle dogs. A bolus injection of isoproterenol increased RV dP/dtmax≈5-fold versus 3-fold in LV.
conclusionCanine RV and LV differ in their β-AR response due to intrinsic differences in myocyte β-AR downstream signaling. Enhanced β-AR responsiveness of the RV results from higher cAMP elevation in the cytoplasm, due to a decreased degradation by PDE3 and PDE4 in the RV compared to the LV.
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