ArticlePLoS computational biology2013
Extraction of sub-microscopic Ca fluxes from blurred and noisy fluorescent indicator images with a detailed model fitting approach.
Article in PLoS computational biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Novel Ca2+ wave mechanisms in cardiac myocytes revealed by multiscale Ca2+ release model.The Journal of general physiology · 2025Article
- Modeling sarcoplasmic reticulum CaBiophysics reports · 2024Article
- CaJournal of molecular and cellular cardiology · 2023Article
- Live-cell photo-activated localization microscopy correlates nanoscale ryanodine receptor configuration to calcium sparks in cardiomyocytes.Nature cardiovascular research · 2023Article
- A Stochastic Spatiotemporal Model of Rat Ventricular Myocyte Calcium Dynamics Demonstrated Necessary Features for Calcium Wave Propagation.Membranes · 2021Article
- Excitatory postsynaptic calcium transients atLearning & memory (Cold Spring Harbor, N.Y.) · 2021Article
- In silico simulations reveal that RYR distribution affects the dynamics of calcium release in cardiac myocytes.The Journal of general physiology · 2021Article
- Effects of rogue ryanodine receptors on CaRoyal Society open science · 2018Article
- The Interplay of Rogue and Clustered Ryanodine Receptors Regulates CaFrontiers in physiology · 2018Article
- Quenching the spark: Termination of CICR in the submicroscopic space of the dyad.The Journal of general physiology · 2017Review
- Perspectives on "Control of Ca release from within the cardiac sarcoplasmic reticulum".The Journal of general physiology · 2017Article
- Ambiguous interactions between diastolic and SR CaThe Journal of general physiology · 2017Review
- Junctophilin-2 in the nanoscale organisation and functional signalling of ryanodine receptor clusters in cardiomyocytes.Journal of cell science · 2016Article
- Length-dependent Ca2+ activation in skeletal muscle fibers from mammalians.American journal of physiology. Cell physiology · 2016Article
- Cellular Hypertrophy and Increased Susceptibility to Spontaneous Calcium-Release of Rat Left Atrial Myocytes Due to Elevated Afterload.PloS one · 2015Article
- Calcium waves initiating from the anomalous subdiffusive calcium sparks.Journal of the Royal Society, Interface · 2014Article
- Life and death of a cardiac calcium spark.The Journal of general physiology · 2013Article
- Control of sarcoplasmic reticulum Ca2+ release by stochastic RyR gating within a 3D model of the cardiac dyad and importance of induction decay for CICR termination.Biophysical journal · 2013Article
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The release of Ca from intracellular stores is key to cardiac muscle function; however, the molecular control of intracellular Ca release remains unclear. Depletion of the intracellular Ca store (sarcoplasmic reticulum, SR) may play an important role, but the ability to measure local SR Ca with fluorescent Ca indicators is limited by the microscope optical resolution and properties of the indicator. This leads to an uncertain degree of spatio-temporal blurring, which is not easily corrected (by deconvolution methods) due to the low signal-to-noise ratio of the recorded signals. In this study, a 3D computer model was constructed to calculate local Ca fluxes and consequent dye signals, which were then blurred by a measured microscope point spread function. Parameter fitting was employed to adjust a release basis function until the model output fitted recorded (2D) Ca spark data. This 'forward method' allowed us to obtain estimates of the time-course of Ca release flux and depletion within the sub-microscopic local SR associated with a number of Ca sparks. While variability in focal position relative to Ca spark sites causes more out-of-focus events to have smaller calculated fluxes (and less SR depletion), the average SR depletion was to 20±10% (s.d.) of the resting level. This focus problem implies that the actual SR depletion is likely to be larger and the five largest depletions analyzed were to 8±6% of the resting level. This profound depletion limits SR release flux during a Ca spark, which peaked at 8±3 pA and declined with a half time of 7±2 ms. By comparison, RyR open probability declined more slowly, suggesting release termination is dominated by neither SR Ca depletion nor intrinsic RyR gating, but results from an interaction of these processes.
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