ArticleJournal of molecular and cellular cardiology2014
Stochasticity intrinsic to coupled-clock mechanisms underlies beat-to-beat variability of spontaneous action potential firing in sinoatrial node pacemaker cells.
Article in Journal of molecular and cellular cardiology, 2014. 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, 43 citations in OpenAlex.
- Sympatho-vagal balance and intrinsic sinoatrial node activity in larval zebrafish quantified by heart rate variability.Scientific reports · 2026Article
- Computational insights on drug effects on intrinsic stochasticity of mouse pacemaker cell activity.Biophysical journal · 2025Article
- Somatodendritic organization of pacemaker activity in midbrain dopamine neurons.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2024Article
- cAMP signaling affects age-associated deterioration of pacemaker beating interval dynamics.GeroScience · 2023Article
- Lipopolysaccharide-induced sepsis impairs M2R-GIRK signaling in the mouse sinoatrial node.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Synergy between Membrane Currents Prevents Severe Bradycardia in Mouse Sinoatrial Node Tissue.International journal of molecular sciences · 2023Article
- The Heart's Pacemaker Mimics Brain Cytoarchitecture and Function: Novel Interstitial Cells Expose Complexity of the SAN.JACC. Clinical electrophysiology · 2022Article
- Biological noise is a key determinant of the reproducibility and adaptability of cardiac pacemaking and EC coupling.The Journal of general physiology · 2022Review
- Adenosine reduces sinoatrial node cell action potential firing rate by uncoupling its membrane and calcium clocks.Frontiers in physiology · 2022Article
- Increase in CaFrontiers in physiology · 2022Article
- Drivers of Sinoatrial Node Automaticity in Zebrafish: Comparison With Mechanisms of Mammalian Pacemaker Function.Frontiers in physiology · 2022Article
- Self-Similar Synchronization of Calcium and Membrane Potential Transitions During Action Potential Cycles Predict Heart Rate Across Species.JACC. Clinical electrophysiology · 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
- Mechanical Communication Acts as a Noise Filter.iScience · 2019Article
- Eliminating contraction during culture maintains global and local CaCell calcium · 2019Article
- Beat-to-Beat Patterning of Sinus Rhythm Reveals Non-linear Rhythm in the Dog Compared to the Human.Frontiers in physiology · 2019Article
- Overexpression of a Neuronal Type Adenylyl Cyclase (Type 8) in Sinoatrial Node Markedly Impacts Heart Rate and Rhythm.Frontiers in neuroscience · 2019Article
- Positive Feedback Mechanisms among Local Ca Releases, NCX, and IBiophysical journal · 2018Article
- Sinoatrial Beat to Beat Variability Assessed by Contraction Strength in Addition to the Interbeat Interval.Frontiers in physiology · 2018Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Recent evidence indicates that the spontaneous action potential (AP) of isolated sinoatrial node cells (SANCs) is regulated by a system of stochastic mechanisms embodied within two clocks: ryanodine receptors of the "Ca(2+) clock" within the sarcoplasmic reticulum, spontaneously activate during diastole and discharge local Ca(2+) releases (LCRs) beneath the cell surface membrane; clock crosstalk occurs as LCRs activate an inward Na(+)/Ca(2+) exchanger current (INCX), which together with If and decay of K(+) channels prompts the "M clock," the ensemble of sarcolemmal-electrogenic molecules, to generate APs. Prolongation of the average LCR period accompanies prolongation of the average AP beating interval (BI). Moreover, the prolongation of the average AP BI accompanies increased AP BI variability. We hypothesized that both the average AP BI and AP BI variability are dependent upon stochasticity of clock mechanisms reported by the variability of LCR period. We perturbed the coupled-clock system by directly inhibiting the M clock by ivabradine (IVA) or the Ca(2+) clock by cyclopiazonic acid (CPA). When either clock is perturbed by IVA (3, 10 and 30 μM), which has no direct effect on Ca(2+) cycling, or CPA (0.5 and 5 μM), which has no direct effect on the M clock ion channels, the clock system failed to achieve the basal AP BI and both AP BI and AP BI variability increased. The changes in average LCR period and its variability in response to perturbations of the coupled-clock system were correlated with changes in AP beating interval and AP beating interval variability. We conclude that the stochasticity within the coupled-clock system affects and is affected by the AP BI firing rate and rhythm via modulation of the effectiveness of clock coupling.
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