ReviewInternational journal of molecular sciences2021
Dual Activation of Phosphodiesterase 3 and 4 Regulates Basal Cardiac Pacemaker Function and Beyond.
Review in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- Sinoatrial Node Impulses Emerge From Unique Synchronization Processing Solutions of Partially Stochastic Local Calcium Signals.JACC. Clinical electrophysiology · 2026Article
- Phosphodiesterase 8 regulation of excitation-contraction coupling as a target for cardiovascular disease: is it my turn now?American journal of physiology. Heart and circulatory physiology · 2026Review
- The Role of PDE3A in Cancer.ACS omega · 2026Review
- Computational insights on drug effects on intrinsic stochasticity of mouse pacemaker cell activity.Biophysical journal · 2025Article
- Longevity mechanisms in cardiac aging: exploring calcium dysregulation and senescence.Biogerontology · 2025Review
- Phosphodiesterase 5 and its inhibitors with ischaemic heart disease: a Mendelian randomization analysis and a real-world study.European heart journal. Cardiovascular pharmacotherapy · 2025Article
- Cantharidin increases the force of contraction and protein phosphorylation in isolated human atria.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Contribution of membrane-associated oscillators to biological timing at different timescales.Frontiers in physiology · 2023Article
- Preferential Expression of CaBiomolecules · 2022Article
- L-Type CaCells · 2022Article
- Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The sinoatrial (SA) node is the physiological pacemaker of the heart, and resting heart rate in humans is a well-known risk factor for cardiovascular disease and mortality. Consequently, the mechanisms of initiating and regulating the normal spontaneous SA node beating rate are of vital importance. Spontaneous firing of the SA node is generated within sinoatrial nodal cells (SANC), which is regulated by the coupled-clock pacemaker system. Normal spontaneous beating of SANC is driven by a high level of cAMP-mediated PKA-dependent protein phosphorylation, which rely on the balance between high basal cAMP production by adenylyl cyclases and high basal cAMP degradation by cyclic nucleotide phosphodiesterases (PDEs). This diverse class of enzymes includes 11 families and PDE3 and PDE4 families dominate in both the SA node and cardiac myocardium, degrading cAMP and, consequently, regulating basal cardiac pacemaker function and excitation-contraction coupling. In this review, we will demonstrate similarities between expression, distribution, and colocalization of various PDE subtypes in SANC and cardiac myocytes of different species, including humans, focusing on PDE3 and PDE4. Here, we will describe specific targets of the coupled-clock pacemaker system modulated by dual PDE3 + PDE4 activation and provide evidence that concurrent activation of PDE3 + PDE4, operating in a synergistic manner, regulates the basal cardiac pacemaker function and provides control over normal spontaneous beating of SANCs through (PDE3 + PDE4)-dependent modulation of local subsarcolemmal Ca
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Registered trials
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