ArticleBiophysical journal2019
Mechanisms of Calcium Leak from Cardiac Sarcoplasmic Reticulum Revealed by Statistical Mechanics.
Article in Biophysical journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- Elementary intracellular Ca signals approximated as a transition of release channel system from a metastable state.Journal of applied physics · 2023Article
- Disorder in Ca2+ release unit locations confers robustness but cuts flexibility of heart pacemaking.The Journal of general physiology · 2022Article
- Phosphorylation of RyR2 Ser-2814 by CaMKII mediates β1-adrenergic stress induced CaFEBS open bio · 2021Article
- In silico simulations reveal that RYR distribution affects the dynamics of calcium release in cardiac myocytes.The Journal of general physiology · 2021Article
- Simulating cardiac CaPflugers Archiv : European journal of physiology · 2021Article
- CaFrontiers in physiology · 2021Article
- Recruiting RyRs to Open in a CaBiophysical journal · 2020Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Heart muscle contraction is normally activated by a synchronized Ca release from sarcoplasmic reticulum (SR), a major intracellular Ca store. However, under abnormal conditions, Ca leaks from the SR, decreasing heart contraction amplitude and increasing risk of life-threatening arrhythmia. The mechanisms and regimes of SR operation generating the abnormal Ca leak remain unclear. Here, we employed both numerical and analytical modeling to get mechanistic insights into the emergent Ca leak phenomenon. Our numerical simulations using a detailed realistic model of the Ca release unit reveal sharp transitions resulting in Ca leak. The emergence of leak is closely mapped mathematically to the Ising model from statistical mechanics. The system steady-state behavior is determined by two aggregate parameters: the analogs of magnetic field (h) and the inverse temperature (β) in the Ising model, for which we have explicit formulas in terms of SR [Ca] and release channel opening and closing rates. The classification of leak regimes takes the shape of a phase β-h diagram, with the regime boundaries occurring at h = 0 and a critical value of β (β
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Registered trials
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