ArticleBiophysical journal2011
Synchronization of stochastic Ca²(+) release units creates a rhythmic Ca²(+) clock in cardiac pacemaker cells.
Article in Biophysical journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 72 citations in OpenAlex.
- Sinoatrial Node Impulses Emerge From Unique Synchronization Processing Solutions of Partially Stochastic Local Calcium Signals.JACC. Clinical electrophysiology · 2026Article
- Beat-locked ATP microdomains in the sinoatrial node map a Ca2+-timed energetic hierarchy and regional pacemaker roles.The Journal of general physiology · 2026Article
- A new Fight-or-Flight Pacemaker Mechanism via Ryanodine Receptor abundance and superclustering.PLoS computational biology · 2026Article
- Structure-Function Relationship of the Ryanodine Receptor Cluster Network in Sinoatrial Node Cells.Cells · 2024Article
- Elementary intracellular Ca signals approximated as a transition of release channel system from a metastable state.Journal of applied physics · 2023Article
- Diversity of cells and signals in the cardiovascular system.The Journal of physiology · 2023Article
- Emergent activity, heterogeneity, and robustness in a calcium feedback model of the sinoatrial node.Biophysical journal · 2023Article
- The Heart's Pacemaker Mimics Brain Cytoarchitecture and Function: Novel Interstitial Cells Expose Complexity of the SAN.JACC. Clinical electrophysiology · 2022Article
- Disorder in Ca2+ release unit locations confers robustness but cuts flexibility of heart pacemaking.The Journal of general physiology · 2022Article
- A variable refractory period increases collective performance in noisy environments.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Self-Similar Synchronization of Calcium and Membrane Potential Transitions During Action Potential Cycles Predict Heart Rate Across Species.JACC. Clinical electrophysiology · 2021Article
- Article
- Random heterogeneity outperforms design in network synchronization.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- CaFrontiers in physiology · 2021Article
- Synchronized Cardiac Impulses Emerge From Heterogeneous Local Calcium Signals Within and Among Cells of Pacemaker Tissue.JACC. Clinical electrophysiology · 2020Article
- The Cardiac Pacemaker Story-Fundamental Role of the NaFrontiers in pharmacology · 2020Review
- Mechanisms of Calcium Leak from Cardiac Sarcoplasmic Reticulum Revealed by Statistical Mechanics.Biophysical journal · 2019Article
- Unique CaInternational journal of molecular sciences · 2018Review
- The role of luminal Ca regulation in Ca signaling refractoriness and cardiac arrhythmogenesis.The Journal of general physiology · 2017Review
- Stabilization of diastolic calcium signal via calcium pump regulation of complex local calcium releases and transient decay in a computational model of cardiac pacemaker cell with individual release channels.PLoS computational biology · 2017Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
In sinoatrial node cells of the heart, beating rate is controlled, in part, by local Ca²(+) releases (LCRs) from the sarcoplasmic reticulum, which couple to the action potential via electrogenic Na(+)/Ca²(+) exchange. We observed persisting, roughly periodic LCRs in depolarized rabbit sinoatrial node cells (SANCs). The features of these LCRs were reproduced by a numerical model consisting of a two-dimensional array of stochastic, diffusively coupled Ca²(+) release units (CRUs) with fixed refractory period. Because previous experimental studies showed that β-adrenergic receptor stimulation increases the rate of Ca²(+) release through each CRU (dubbed I(spark)), we explored the link between LCRs and I(spark) in our model. Increasing the CRU release current I(spark) facilitated Ca²(+)-induced-Ca²(+) release and local recruitment of neighboring CRUs to fire more synchronously. This resulted in a progression in simulated LCR size (from sparks to wavelets to global waves), LCR rhythmicity, and decrease of LCR period that parallels the changes observed experimentally with β-adrenergic receptor stimulation. The transition in LCR characteristics was steeply nonlinear over a narrow range of I(spark), resembling a phase transition. We conclude that the (partial) periodicity and rate regulation of the "Calcium clock" in SANCs are emergent properties of the diffusive coupling of an ensemble of interacting stochastic CRUs. The variation in LCR period and size with I(spark) is sufficient to account for β-adrenergic regulation of SANC beating rate.
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