ReviewCirculation research2010
A coupled SYSTEM of intracellular Ca2+ clocks and surface membrane voltage clocks controls the timekeeping mechanism of the heart's pacemaker.
Review in Circulation research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 387 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
387 citing papers in PubMed, 620 citations in OpenAlex.
- Heme oxygenase/carbon monoxide system and cardiac conduction system.Medical gas research · 2026Review
- Order From Noise: What the Pacemaker Pays for Stochastic Resonance.Circulation research · 2026Article
- Sinoatrial Node Impulses Emerge From Unique Synchronization Processing Solutions of Partially Stochastic Local Calcium Signals.JACC. Clinical electrophysiology · 2026Article
- Cardiac function in zebrafish embryos is linked to an androgen receptor-adrenomedullin-proepicardium axis.Cell communication and signaling : CCS · 2026Article
- Intracellular CaInternational journal of molecular sciences · 2026Article
- cAMP-Activated EPAC Signaling Is an Integral Component of Cardiac Pacemaker Cell Automaticity.Circulation. Arrhythmia and electrophysiology · 2026Article
- The cardiac pacemakers: A paradigm of robustness in evolutionary biology.The Journal of physiology · 2026Review
- Regulation of Pacemaker Current in the Sinoatrial Node by Zonula Occludens-1.bioRxiv : the preprint server for biology · 2026Article
- Aglianico Grape Pomace Extract Reduces Cardiac Pacemaker Activity by Decreasing Hyperpolarization-Activated Current Density Independently of cAMP Signaling.Life (Basel, Switzerland) · 2026Article
- Biomechanical Isolation is Required for Maintenance of the Cardiac Pacemaker Cell Fate.Research square · 2026Article
- Cardiac Pacemaker Cells Harness Stochastic Resonance to Ensure Fail-Safe Operation at Low Rates Bordering on Sinus Arrest.bioRxiv : the preprint server for biology · 2026Article
- A new Fight-or-Flight Pacemaker Mechanism via Ryanodine Receptor abundance and superclustering.PLoS computational biology · 2026Article
- Pacemaking in the lymphatic system.The Journal of physiology · 2026Review
- The cardiac conduction system: development, function and therapeutic targets.Nature reviews. Cardiology · 2026Review
- Caveolar Compartmentalization of Pacemaker Signaling Ensures Stable Sinoatrial Rhythmicity Which Is Disrupted in Heart Failure.JACC. Clinical electrophysiology · 2026Article
- Pacemaking in the heart: a redundant and robust system of mutually entrained oscillators driving cardiac automaticity.The Journal of physiology · 2026Review
- Emerging Regulatory Mechanisms in Sinoatrial Node Automaticity.Journal of cellular and molecular medicine · 2026Review
- Molecular Symphony of Sympathetic Acceleration: Reframing the Pacemaker Paradigm.Circulation research · 2026Article
- L-Type CaCirculation research · 2026Article
- Heart rate fragmentation as a marker of autonomic function in healthy young individuals: insights from graded head-up tilt test and controlled breathing.Frontiers in physiology · 2026Article
327 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Ion channels on the surface membrane of sinoatrial nodal pacemaker cells (SANCs) are the proximal cause of an action potential. Each individual channel type has been thoroughly characterized under voltage clamp, and the ensemble of the ion channel currents reconstructed in silico generates rhythmic action potentials. Thus, this ensemble can be envisioned as a surface "membrane clock" (M clock). Localized subsarcolemmal Ca(2+) releases are generated by the sarcoplasmic reticulum via ryanodine receptors during late diastolic depolarization and are referred to as an intracellular "Ca(2+) clock," because their spontaneous occurrence is periodic during voltage clamp or in detergent-permeabilized SANCs, and in silico as well. In spontaneously firing SANCs, the M and Ca(2+) clocks do not operate in isolation but work together via numerous interactions modulated by membrane voltage, subsarcolemmal Ca(2+), and protein kinase A and CaMKII-dependent protein phosphorylation. Through these interactions, the 2 subsystem clocks become mutually entrained to form a robust, stable, coupled-clock system that drives normal cardiac pacemaker cell automaticity. G protein-coupled receptors signaling creates pacemaker flexibility, ie, effects changes in the rhythmic action potential firing rate, by impacting on these very same factors that regulate robust basal coupled-clock system function. This review examines evidence that forms the basis of this coupled-clock system concept in cardiac SANCs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.