ArticleBiophysical journal2011
How does stochastic ryanodine receptor-mediated Ca leak fail to initiate a Ca spark?
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 47 papers.
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Who cites it
47 citing papers in PubMed.
- Gerrymandering in the heart: How tissue heterogeneities promote premature ventricular contractions.Biophysical journal · 2026Article
- Mechanisms underlying local CaThe Journal of physiology · 2025Article
- Role of ryanodine receptor cooperativity in CaThe Journal of physiology · 2024Article
- Computational Modeling of Cardiac Electrophysiology.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Elementary intracellular Ca signals approximated as a transition of release channel system from a metastable state.Journal of applied physics · 2023Article
- Mechanisms of spontaneous CaThe Journal of physiology · 2023Article
- Mechanisms of spontaneous CaThe Journal of physiology · 2023Article
- Preserved cardiac performance and adrenergic response in a rabbit model with decreased ryanodine receptor 2 expression.Journal of molecular and cellular cardiology · 2022Article
- Multi-Scale Computational Modeling of Spatial Calcium Handling From Nanodomain to Whole-Heart: Overview and Perspectives.Frontiers in physiology · 2022Review
- Three-Dimensional Model of Sub-Plasmalemmal CaFrontiers in molecular biosciences · 2022Article
- Increasing SERCA function promotes initiation of calcium sparks and breakup of calcium waves.The Journal of physiology · 2021Article
- Recruiting RyRs to Open in a CaBiophysical journal · 2020Article
- Mechanisms of Calcium Leak from Cardiac Sarcoplasmic Reticulum Revealed by Statistical Mechanics.Biophysical journal · 2019Article
- Size Matters: Ryanodine Receptor Cluster Size Heterogeneity Potentiates Calcium Waves.Biophysical journal · 2019Article
- NCX-Mediated Subcellular CaBiophysical journal · 2018Article
- Size Matters: Ryanodine Receptor Cluster Size Affects Arrhythmogenic Sarcoplasmic Reticulum Calcium Release.Journal of the American Heart Association · 2018Article
- Effects of rogue ryanodine receptors on CaRoyal Society open science · 2018Article
- The Interplay of Rogue and Clustered Ryanodine Receptors Regulates CaFrontiers in physiology · 2018Article
- A model for cooperative gating of L-type Ca2+ channels and its effects on cardiac alternans dynamics.PLoS computational biology · 2018Article
- Calcium-Dependent Arrhythmogenic Foci Created by Weakly Coupled Myocytes in the Failing Heart.Circulation research · 2017Article
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2 authors.
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Abstract
Spontaneous calcium (Ca) sparks are initiated by single ryanodine receptor (RyR) opening. Once one RyR channel opens, it elevates local [Ca] in the cleft space ([Ca](Cleft)), which opens other RyR channels in the same Ca release unit (CaRU) via Ca-induced Ca-release. Experiments by Zima et al. (J. Physiol. 588:4743-4757, 2010) demonstrate that spontaneous Ca sparks occur only when intrasarcoplasmic-reticulum (SR) [Ca] ([Ca](SR)) is above a threshold level, but that RyR-mediated SR Ca leak exists without Ca sparks well below this threshold [Ca](SR). We examine here how single RyR opening at lower [Ca](SR) can fail to recruit Ca sparks at a CaRU, while still contributing to SR Ca leak. We assess this using a physiologically detailed mathematical model of junctional SR Ca release in which RyR gating is regulated by [Ca](SR) and [Ca](Cleft). We find that several factors contribute to the failure of Ca sparks as [Ca](SR) declines: 1), lower [Ca](SR) reduces driving force and thus limits local [Ca](Cleft) achieved and the rate of rise during RyR opening; 2), low [Ca](SR) limits RyR open time (τ(O)), which further reduces local [Ca](Cleft) attained; 3), low τ(O) and fast [Ca](Cleft) dissipation after RyR closure shorten the opportunity for neighboring RyR activation; 4), at low [Ca](SR), the RyR exhibits reduced [Ca](Cleft) sensitivity. We conclude that all of these factors conspire to reduce the probability of Ca sparks as [Ca](SR) declines, despite continued RyR-mediated Ca leak. In addition, these same factors explain the much lower efficacy of L-type Ca channel opening to trigger local SR Ca release at low [Ca](SR) during excitation-contraction coupling. Conversely, all of these factors are fundamentally important for increasing the propensity for pro-arrhythmic Ca sparks and waves in cardiac myocytes at high [Ca](SR).
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