ArticlePLoS computational biology2010
Numerical analysis of Ca2+ signaling in rat ventricular myocytes with realistic transverse-axial tubular geometry and inhibited sarcoplasmic reticulum.
Article in PLoS computational biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Electrodiffusion dynamics in the cardiomyocyte dyad at nano-scale resolution using the Poisson-Nernst-Planck (PNP) equations.PLoS computational biology · 2025Article
- Multi-Scale Computational Modeling of Spatial Calcium Handling From Nanodomain to Whole-Heart: Overview and Perspectives.Frontiers in physiology · 2022Review
- An Open-Source Mesh Generation Platform for Biophysical Modeling Using Realistic Cellular Geometries.Biophysical journal · 2020Article
- Applications and Challenges of Machine Learning to Enable Realistic Cellular Simulations.Frontiers in physics · 2020Article
- Transverse tubular network structures in the genesis of intracellular calcium alternans and triggered activity in cardiac cells.Journal of molecular and cellular cardiology · 2018Article
- A computational model of spatio-temporal cardiac intracellular calcium handling with realistic structure and spatial flux distribution from sarcoplasmic reticulum and t-tubule reconstructions.PLoS computational biology · 2017Article
- Numerical Approach to Spatial Deterministic-Stochastic Models Arising in Cell Biology.PLoS computational biology · 2016Article
- Hybrid finite element and Brownian dynamics method for charged particles.The Journal of chemical physics · 2016Article
- Examination of the Effects of Heterogeneous Organization of RyR Clusters, Myofibrils and Mitochondria on Ca2+ Release Patterns in Cardiomyocytes.PLoS computational biology · 2015Article
- Revealing T-Tubules in Striated Muscle with New Optical Super-Resolution Microscopy Techniquess.European journal of translational myology · 2015Review
- An integrated finite element simulation of cardiomyocyte function based on triphasic theory.Frontiers in physiology · 2015Article
- Effect of Alcohol Administration on MgJournal of cardiovascular diseases & diagnosis · 2014Article
- Predicting the influence of long-range molecular interactions on macroscopic-scale diffusion by homogenization of the Smoluchowski equation.The Journal of chemical physics · 2014Article
- Computational modeling of subcellular transport and signaling.Current opinion in structural biology · 2014Review
- Numerical analysis of the effect of T-tubule location on calcium transient in ventricular myocytes.Bio-medical materials and engineering · 2014Article
- Evoked centripetal Ca(2+) mobilization in cardiac Purkinje cells: insight from a model of three Ca(2+) release regions.The Journal of physiology · 2013Article
- Decoding myocardial Ca²⁺ signals across multiple spatial scales: a role for sensitivity analysis.Journal of molecular and cellular cardiology · 2013Review
- Alterations in T-tubule and dyad structure in heart disease: challenges and opportunities for computational analyses.Cardiovascular research · 2013Review
- Sensitivity of rabbit ventricular action potential and Ca²⁺ dynamics to small variations in membrane currents and ion diffusion coefficients.BioMed research international · 2013Article
- Hybrid finite element and Brownian dynamics method for diffusion-controlled reactions.The Journal of chemical physics · 2012Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The t-tubules of mammalian ventricular myocytes are invaginations of the cell membrane that occur at each Z-line. These invaginations branch within the cell to form a complex network that allows rapid propagation of the electrical signal, and hence synchronous rise of intracellular calcium (Ca(2+)). To investigate how the t-tubule microanatomy and the distribution of membrane Ca(2+) flux affect cardiac excitation-contraction coupling we developed a 3-D continuum model of Ca(2+) signaling, buffering and diffusion in rat ventricular myocytes. The transverse-axial t-tubule geometry was derived from light microscopy structural data. To solve the nonlinear reaction-diffusion system we extended SMOL software tool (http://mccammon.ucsd.edu/smol/). The analysis suggests that the quantitative understanding of the Ca(2+) signaling requires more accurate knowledge of the t-tubule ultra-structure and Ca(2+) flux distribution along the sarcolemma. The results reveal the important role for mobile and stationary Ca(2+) buffers, including the Ca(2+) indicator dye. In agreement with experiment, in the presence of fluorescence dye and inhibited sarcoplasmic reticulum, the lack of detectible differences in the depolarization-evoked Ca(2+) transients was found when the Ca(2+) flux was heterogeneously distributed along the sarcolemma. In the absence of fluorescence dye, strongly non-uniform Ca(2+) signals are predicted. Even at modest elevation of Ca(2+), reached during Ca(2+) influx, large and steep Ca(2+) gradients are found in the narrow sub-sarcolemmal space. The model predicts that the branched t-tubule structure and changes in the normal Ca(2+) flux density along the cell membrane support initiation and propagation of Ca(2+) waves in rat myocytes.
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Registered trials
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