ArticleCirculation research2013
RyR-NCX-SERCA local cross-talk ensures pacemaker cell function at rest and during the fight-or-flight reflex.
Article in Circulation research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Regulation of Pacemaker Current in the Sinoatrial Node by Zonula Occludens-1.bioRxiv : the preprint server for biology · 2026Article
- A new Fight-or-Flight Pacemaker Mechanism via Ryanodine Receptor abundance and superclustering.PLoS computational biology · 2026Article
- Caveolar Compartmentalization of Pacemaker Signaling Ensures Stable Sinoatrial Rhythmicity Which Is Disrupted in Heart Failure.JACC. Clinical electrophysiology · 2026Article
- Structure-Function Relationship of the Ryanodine Receptor Cluster Network in Sinoatrial Node Cells.Cells · 2024Article
- Modeling Calcium Cycling in the Heart: Progress, Pitfalls, and Challenges.Biomolecules · 2022Review
- Disorder in Ca2+ release unit locations confers robustness but cuts flexibility of heart pacemaking.The Journal of general physiology · 2022Article
- Speeding Up the Heart? Traditional and New Perspectives on HCN4 Function.Frontiers in physiology · 2021Review
- Article
- Na/Ca exchange in the atrium: Role in sinoatrial node pacemaking and excitation-contraction coupling.Cell calcium · 2020Review
- 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
- Positive Feedback Mechanisms among Local Ca Releases, NCX, and IBiophysical journal · 2018Article
- Polycystin 2-dependent cardio-protective mechanisms revealed by cardiac stress.Pflugers Archiv : European journal of physiology · 2017Article
- 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
- Clusters of calcium release channels harness the Ising phase transition to confine their elementary intracellular signals.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Computer algorithms for automated detection and analysis of local Ca2+ releases in spontaneously beating cardiac pacemaker cells.PloS one · 2017Article
- Ca(2+)/calmodulin-activated phosphodiesterase 1A is highly expressed in rabbit cardiac sinoatrial nodal cells and regulates pacemaker function.Journal of molecular and cellular cardiology · 2016Article
- STIM1-Ca2+ signaling modulates automaticity of the mouse sinoatrial node.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Potential effects of intrinsic heart pacemaker cell mechanisms on dysrhythmic cardiac action potential firing.Frontiers in physiology · 2015Article
- Effectiveness of gene delivery systems for pluripotent and differentiated cells.Molecular therapy. Methods & clinical development · 2015Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
rationaleA recent study published in Circulation Research by Gao et al used sinoatrial node (SAN)-targeted, incomplete Ncx1 knockout in mice to explore the role of the Na(+)/Ca(2+) exchanger (NCX) in cardiac pacemaker. The authors concluded that NCX is required for increasing sinus rates, but not for maintaining resting heart rate. This conclusion was based, in part, on numeric model simulations performed by Gao et al that reproduced their experimental results of unchanged action potentials in the knockout SAN cells. The authors, however, did not simulate the NCX current (INCX), that is, the subject of the study.
objectiveWe extended numeric examinations to simulate INCX in their incomplete knockout SAN cells that is crucial to interpret the study results. METHODS AND
resultsINCX and Ca(2+) dynamics were simulated using different contemporary numeric models of SAN cells. We found that minimum diastolic Ca(2+) levels and INCX amplitudes generated by remaining NCX molecules (only 20% of control) remained almost unchanged. Simulations using a new local Ca(2+) control model indicate that these powerful compensatory mechanisms involve complex local cross-talk of Ca(2+) cycling proteins and NCX. Specifically, lower NCX expression facilitates Ca(2+)-induced Ca(2+) release and larger local Ca(2+) releases that stabilize diastolic INCX. Further reduction of NCX expression results in arrhythmia and halt of automaticity.
conclusionsRemaining NCX molecules in the incomplete knockout model likely produce almost the same diastolic INCX as in wild-type cells. INCX contribution is crucially important for both basal automaticity of SAN cells and during the fight-or-flight reflex.
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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.