ReviewAnnals of the New York Academy of Sciences2008
The missing link in the mystery of normal automaticity of cardiac pacemaker cells.
Review in Annals of the New York Academy of Sciences, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Publication guidelines for human heart rate and heart rate variability studies in psychophysiology-Part 1: Physiological underpinnings and foundations of measurement.Psychophysiology · 2024Guideline
- Regulation of Pacemaker Current in the Sinoatrial Node by Zonula Occludens-1.bioRxiv : the preprint server for biology · 2026Article
- Pacemaking in the heart: a redundant and robust system of mutually entrained oscillators driving cardiac automaticity.The Journal of physiology · 2026Review
- CaPhysiological reviews · 2024Review
- The Dysfunction of CaInternational journal of molecular sciences · 2023Review
- Article
- Drivers of Sinoatrial Node Automaticity in Zebrafish: Comparison With Mechanisms of Mammalian Pacemaker Function.Frontiers in physiology · 2022Article
- What keeps us ticking? Sinoatrial node mechano-sensitivity: the grandfather clock of cardiac rhythm.Biophysical reviews · 2021Review
- CaFrontiers in physiology · 2021Article
- Neurohumoral Control of Sinoatrial Node Activity and Heart Rate: Insight From Experimental Models and Findings From Humans.Frontiers in physiology · 2020Review
- Spontaneous, local diastolic subsarcolemmal calcium releases in single, isolated guinea-pig sinoatrial nodal cells.PloS one · 2017Article
- Electrochemical Na+ and Ca2+ gradients drive coupled-clock regulation of automaticity of isolated rabbit sinoatrial nodal pacemaker cells.American journal of physiology. Heart and circulatory physiology · 2016Article
- From beat rate variability in induced pluripotent stem cell-derived pacemaker cells to heart rate variability in human subjects.Heart rhythm · 2014Article
- Integrating beat rate variability: from single cells to hearts.Heart rhythm · 2013Article
- Intracardiac origin of heart rate variability, pacemaker funny current and their possible association with critical illness.Current cardiology reviews · 2013Review
- Genetic inhibition of Na+-Ca2+ exchanger current disables fight or flight sinoatrial node activity without affecting resting heart rate.Circulation research · 2013Article
- A mathematical model of action potentials of mouse sinoatrial node cells with molecular bases.American journal of physiology. Heart and circulatory physiology · 2011Article
- Rhythmic beating of stem cell-derived cardiac cells requires dynamic coupling of electrophysiology and Ca cycling.Journal of molecular and cellular cardiology · 2011Article
- Expression and roles of Cav1.3 (α1D) L-type Ca²+ channel in atrioventricular node automaticity.Journal of molecular and cellular cardiology · 2011Article
- Stochastic hybrid modeling of intracellular calcium dynamics.The Journal of chemical physics · 2010Article
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 1 institution in 1 country.
Funding
Abstract
Earlier studies of the initiating event of normal automaticity of the heart's pacemaker cells, inspired by classical quantitative membrane theory, focused upon ion currents (IK, I f) that determine the maximum diastolic potential and the early phase of the spontaneous diastolic depolarization (DD). These early DD events are caused by the prior action potential (AP) and essentially reflect a membrane recovery process. Events following the recovery process that ignite APs have not been recognized and remained a mystery until recently. These critical events are linked to rhythmic intracellular signals initiated by Ca2+ clock (i.e., sarcoplasmic reticulum [SR] cycling Ca2+). Sinoatrial cells, regardless of size, exhibit intense ryanodine receptor (RyR), Na+/Ca2+ exchange (NCX)-1, and SR Ca2+ ATPase-2 immunolabeling and dense submembrane NCX/RyR colocalization; Ca2+ clocks generate spontaneous stochastic but roughly periodic local subsarcolemmal Ca2+ releases (LCR). LCRs generate inward currents via NCX that exponentially accelerate the late DD. The timing and amplitude of LCR/I NCX-coupled events control the timing and amplitude of the nonlinear terminal DD and therefore ultimately control the chronotropic state by determining the timing of the I CaL activation that initiates the next AP. LCR period is precisely controlled by the kinetics of SR Ca2+ cycling, which, in turn, are regulated by 1) the status of protein kinase A-dependent phosphorylation of SR Ca2+ cycling proteins; and 2) membrane ion channels ensuring the Ca2+ homeostasis and therefore the Ca2+ available to Ca2+ clock. Thus, the link between early DD and next AP, missed in earlier studies, is ensured by a precisely physiologically regulated Ca2+ clock within pacemaker cells that integrates multiple Ca2+-dependent functions and rhythmically ignites APs during late DD via LCRs-I NCX coupling.
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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.