ArticleScience signaling2013
Ca²⁺-dependent phosphorylation of Ca²⁺ cycling proteins generates robust rhythmic local Ca²⁺ releases in cardiac pacemaker cells.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Potential roles of β3-adrenergic receptor in heart rate regulation via sinus node activity and local adipocyte metabolism.The journal of physiological sciences : JPS · 2026Article
- cAMP-Activated EPAC Signaling Is an Integral Component of Cardiac Pacemaker Cell Automaticity.Circulation. Arrhythmia and electrophysiology · 2026Article
- Beyond neurotransmission: the roles of serotonylation in physiological and pathological processes.Cellular & molecular biology letters · 2026Review
- CaCells · 2024Review
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- What makes the sinoatrial node tick? A question not for the faint of heart.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- A novel small positive allosteric modulator of neuropeptide receptor PAC1-R exerts neuroprotective effects in MPTP mouse Parkinson's disease model.Acta biochimica et biophysica Sinica · 2022Article
- The paradigm shift: Heartbeat initiation without "the pacemaker cell".Frontiers in physiology · 2022Article
- Article
- What keeps us ticking? Sinoatrial node mechano-sensitivity: the grandfather clock of cardiac rhythm.Biophysical reviews · 2021Review
- Dual Activation of Phosphodiesterase 3 and 4 Regulates Basal Cardiac Pacemaker Function and Beyond.International journal of molecular sciences · 2021Review
- cAMP-Dependent Signaling Restores AP Firing in Dormant SA Node Cells via Enhancement of Surface Membrane Currents and Calcium Coupling.Frontiers in physiology · 2021Article
- CaFrontiers in physiology · 2021Article
- Signatures of the autonomic nervous system and the heart's pacemaker cells in canine electrocardiograms and their applications to humans.Scientific reports · 2020Article
- Neurohumoral Control of Sinoatrial Node Activity and Heart Rate: Insight From Experimental Models and Findings From Humans.Frontiers in physiology · 2020Review
- The Cardiac Pacemaker Story-Fundamental Role of the NaFrontiers in pharmacology · 2020Review
- Eliminating contraction during culture maintains global and local CaCell calcium · 2019Article
- Unique CaInternational journal of molecular sciences · 2018Review
- A coupled-clock system drives the automaticity of human sinoatrial nodal pacemaker cells.Science signaling · 2018Article
- Basal Spontaneous Firing of Rabbit Sinoatrial Node Cells Is Regulated by Dual Activation of PDEs (Phosphodiesterases) 3 and 4.Circulation. Arrhythmia and electrophysiology · 2018Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The spontaneous beating of the heart is governed by spontaneous firing of sinoatrial node cells, which generate action potentials due to spontaneous depolarization of the membrane potential, or diastolic depolarization. The spontaneous diastolic depolarization rate is determined by spontaneous local submembrane Ca²⁺ releases through ryanodine receptors (RyRs). We sought to identify specific mechanisms of intrinsic Ca²⁺ cycling by which sinoatrial node cells, but not ventricular myocytes, generate robust, rhythmic local Ca²⁺ releases. At similar physiological intracellular Ca²⁺ concentrations, local Ca²⁺ releases were large and rhythmic in permeabilized sinoatrial node cells but small and random in permeabilized ventricular myocytes. Furthermore, sinoatrial node cells spontaneously released more Ca²⁺ from the sarcoplasmic reticulum than did ventricular myocytes, despite comparable sarcoplasmic reticulum Ca²⁺ content in both cell types. This ability of sinoatrial node cells to generate larger and rhythmic local Ca²⁺ releases was associated with increased abundance of sarcoplasmic reticulum Ca²⁺-ATPase (SERCA), reduced abundance of the SERCA inhibitor phospholamban, and increased Ca²⁺-dependent phosphorylation of phospholamban and RyR. The increased phosphorylation of RyR in sinoatrial node cells may facilitate Ca²⁺ release from the sarcoplasmic reticulum, whereas Ca²⁺-dependent increase in phosphorylation of phospholamban relieves its inhibition of SERCA, augmenting the pumping rate of Ca²⁺ required to support robust, rhythmic local Ca²⁺ releases. The differences in Ca²⁺ cycling between sinoatrial node cells and ventricular myocytes provide insights into the regulation of intracellular Ca²⁺ cycling that drives the automaticity of sinoatrial node cells.
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