Publications
Journal Article
Arrhythmogenic influence of mutations in a myocyte‑based computational model of the pulmonary vein sleeve
Nature Scientific Reports 12 (2022): 7040.Status: Published
Arrhythmogenic influence of mutations in a myocyte‑based computational model of the pulmonary vein sleeve
In the heart, electrophysiological dysregulation arises from defects at many biological levels (from point mutations in ion channel proteins to gross structural abnormalities). These defects disrupt the normal pattern of electrical activation, producing ectopic activity and reentrant arrhythmia. To interrogate mechanisms that link these primary biological defects to macroscopic electrophysiologic dysregulation most prior computational studies have utilized either (i) detailed models of myocyte ion channel dynamics at limited spatial scales, or (ii) homogenized models of action potential conduction that reproduce arrhythmic activity at tissue and organ levels. Here we apply our recent model (EMI), which integrates electrical activation and propagation across these scales, to study human atrial arrhythmias originating in the pulmonary vein (PV) sleeves. These small structures initiate most supraventricular arrhythmias and include pronounced myocyte‑to‑myocyte heterogeneities in ion channel expression and intercellular coupling. To test EMI’s cell‑based architecture in this physiological context we asked whether ion channel mutations known to underlie atrial fibrillation are capable of initiating arrhythmogenic behavior via increased excitability or reentry in a schematic PV sleeve geometry. Our results illustrate that EMI’s improved spatial resolution can directly interrogate how electrophysiological changes at the individual myocyte level manifest in tissue and as arrhythmia in the PV sleeve.
Afilliation | Scientific Computing |
Project(s) | Department of Computational Physiology |
Publication Type | Journal Article |
Year of Publication | 2022 |
Journal | Nature Scientific Reports |
Volume | 12 |
Pagination | 7040 |
Publisher | Springer Nature |
URL | https://rdcu.be/cMntU |
DOI | 10.1038/s41598-022-11110-1 |
Journal Article
A computational method for identifying an optimal combination of existing drugs to repair the action potentials of SQT1 ventricular myocytes
PLoS Computational Biology 17 (2021): e1009233.Status: Published
A computational method for identifying an optimal combination of existing drugs to repair the action potentials of SQT1 ventricular myocytes
Mutations are known to cause perturbations in essential functional features of integral membrane proteins, including ion channels. Even restricted or point mutations can result in substantially changed properties of ion currents. The additive effect of these alterations for a specific ion channel can result in significantly changed properties of the action potential (AP). Both AP shortening and AP prolongation can result from known mutations, and the consequences can be life-threatening. Here, we present a computational method for identifying new drugs utilizing combinations of existing drugs. Based on the knowledge of theoretical effects of existing drugs on individual ion currents, our aim is to compute optimal combinations that can ‘repair’ the mutant AP waveforms so that the baseline AP-properties are restored. More specifically, we compute optimal, combined, drug concentrations such that the waveforms of the transmembrane potential and the cytosolic calcium concentration of the mutant cardiomyocytes (CMs) becomes as similar as possible to their wild type coun- terparts after the drug has been applied. In order to demonstrate the utility of this method, we address the question of computing an optimal drug for the short QT syndrome type 1 (SQT1). For the SQT1 mutation N588K, there are available data sets that describe the effect of various drugs on the mutated K+ channel. These published findings are the basis for our computational analysis which can identify optimal compounds in the sense that the AP of the mutant CMs resembles essential biomarkers of the wild type CMs. Using recently developed insights regarding electrophysiological properties among myocytes from different species, we compute optimal drug combinations for hiPSC-CMs, rabbit ventricular CMs and adult human ventricular CMs with the SQT1 mutation. Since the ‘composition’ of ion channels that form the AP is different for the three types of myocytes under consideration, so is the composition of the optimal drug.
Afilliation | Scientific Computing |
Project(s) | Department of Computational Physiology |
Publication Type | Journal Article |
Year of Publication | 2021 |
Journal | PLoS Computational Biology |
Volume | 17 |
Number | 8 |
Pagination | e1009233 |
Publisher | Public Library of Science |
DOI | 10.1371/journal.pcbi.1009233 |
From Millimeters to Micrometers; Re-introducing Myocytes in Models of Cardiac Electrophysiology
Frontiers in Physiology 12 (2021): 763584.Status: Published
From Millimeters to Micrometers; Re-introducing Myocytes in Models of Cardiac Electrophysiology
Computational modeling has contributed significantly to present understanding of cardiac electrophysiology including cardiac conduction, excitation-contraction coupling, and the effects and side-effects of drugs. However, the accuracy of in silico analysis of electrochemical wave dynamics in cardiac tissue is limited by the homogenization procedure (spatial averaging) intrinsic to standard continuum models of conduction. Averaged models cannot resolve the intricate dynamics in the vicinity of individual cardiomyocytes simply because the myocytes are not present in these models. Here we demonstrate how recently developed mathematical models based on representing every myocyte can significantly increase the accuracy, and thus the utility of modeling electrophysiological function and dysfunction in collections of coupled cardiomyocytes. The present gold standard of numerical simulation for cardiac electrophysiology is based on the bidomain model. In the bidomain model, the extracellular (E) space, the cell membrane (M) and the intracellular (I) space are all assumed to be present everywhere in the tissue. Consequently, it is impossible to study biophysical processes taking place close to individual myocytes. The bidomain model represents the tissue by averaging over several hundred myocytes and this inherently limits the accuracy of the model. In our alternative approach both E, M, and I are represented in the model which is therefore referred to as the EMI model. The EMI model approach allows for detailed analysis of the biophysical processes going on in functionally important spaces very close to individual myocytes, although at the cost of significantly increased CPU-requirements.
Afilliation | Scientific Computing |
Project(s) | Department of Computational Physiology |
Publication Type | Journal Article |
Year of Publication | 2021 |
Journal | Frontiers in Physiology |
Volume | 12 |
Pagination | 763584 |
Publisher | Frontiers |
URL | https://www.frontiersin.org/articles/10.3389/fphys.2021.763584/full |
DOI | 10.3389/fphys.2021.763584 |
Heart Muscle Microphysiological System for Cardiac Liability Prediction of Repurposed COVID-19 Therapeutics
Frontiers in Pharmacology 12 (2021): 684252.Status: Published
Heart Muscle Microphysiological System for Cardiac Liability Prediction of Repurposed COVID-19 Therapeutics
Afilliation | Scientific Computing |
Project(s) | IdentiPhy |
Publication Type | Journal Article |
Year of Publication | 2021 |
Journal | Frontiers in Pharmacology |
Volume | 12 |
Pagination | 684252 |
Publisher | Frontiers Media SA |
URL | doi.org/10.3389/fphar.2021.684252 |
DOI | 10.3389/fphar.2021.684252 |
In vitro safety “clinical trial” of the cardiac liability of drug polytherapy
Clinical and Translational Science 14, no. 3 (2021): 1155-1165.Status: Published
In vitro safety “clinical trial” of the cardiac liability of drug polytherapy
Afilliation | Scientific Computing |
Project(s) | IdentiPhy |
Publication Type | Journal Article |
Year of Publication | 2021 |
Journal | Clinical and Translational Science |
Volume | 14 |
Issue | 3 |
Pagination | 1155-1165 |
Date Published | 03/2021 |
Publisher | Wiley Online Library |
URL | https://ascpt.onlinelibrary.wiley.com/doi/full/10.1111/cts.13038 |
DOI | 10.1111/cts.13038 |
Book Chapter
Calcium Signaling in Cardiomyocyte Models With Realistic Geometries
In Zipes and Jalife's Cardiac Electrophysiology: From Cell to Bedside, 362-375. 8th ed. Vol. 1. Elsevier, 2021.Status: Published
Calcium Signaling in Cardiomyocyte Models With Realistic Geometries
Afilliation | Scientific Computing |
Project(s) | Department of Computational Physiology |
Publication Type | Book Chapter |
Year of Publication | 2021 |
Book Title | Zipes and Jalife's Cardiac Electrophysiology: From Cell to Bedside |
Volume | 1 |
Number of Volumes | 1 |
Edition | 8 |
Chapter | 32 |
Pagination | 362-375 |
Date Published | 12/2021 |
Publisher | Elsevier |
Journal Article
A computational study on integrated mechanisms of mechano-electric feedback in ischemic arrhythmogenesis
SAGE (2020).Status: Submitted
A computational study on integrated mechanisms of mechano-electric feedback in ischemic arrhythmogenesis
Afilliation | Scientific Computing |
Project(s) | Department of Computational Physiology |
Publication Type | Journal Article |
Year of Publication | 2020 |
Journal | SAGE |
Publisher | Clinical Medicine Insights: Cardiology |
In Vitro Safety “Clinical Trial” of the Cardiac Liability of Hydroxychloroquine and Azithromycin as COVID19 Polytherapy
Clinical Pharmacology & Therapeutics (2020).Status: Published
In Vitro Safety “Clinical Trial” of the Cardiac Liability of Hydroxychloroquine and Azithromycin as COVID19 Polytherapy
Afilliation | Scientific Computing |
Project(s) | Department of Computational Physiology, IdentiPhy |
Publication Type | Journal Article |
Year of Publication | 2020 |
Journal | Clinical Pharmacology & Therapeutics |
Publisher | Wiley |
Journal Article
3D dSTORM imaging reveals novel detail of ryanodine receptor localization in rat cardiac myocytes
The Journal of Physiology 597, no. 2 (2019): 399-418.Status: Published
3D dSTORM imaging reveals novel detail of ryanodine receptor localization in rat cardiac myocytes
Afilliation | Scientific Computing |
Project(s) | No Simula project |
Publication Type | Journal Article |
Year of Publication | 2019 |
Journal | The Journal of Physiology |
Volume | 597 |
Issue | 2 |
Pagination | 399-418 |
Date Published | Jan-15-2019 |
Publisher | Wiley-Blackwell |
URL | https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP277360 |
DOI | 10.1113/jp277360 |
Arrhythmogenic current generation by myofilament-triggered Ca2+ release and sarcomere heterogeneity
Biophysical Journal 117, no. 12 (2019): 2471-2485.Status: Published
Arrhythmogenic current generation by myofilament-triggered Ca2+ release and sarcomere heterogeneity
Afilliation | Scientific Computing |
Project(s) | Department of Computational Physiology |
Publication Type | Journal Article |
Year of Publication | 2019 |
Journal | Biophysical Journal |
Volume | 117 |
Issue | 12 |
Pagination | 2471-2485 |
Publisher | Cell Press |
Properties of cardiac conduction in a cell-based computational model
PLoS Computational Biology 15, no. 5 (2019).Status: Published
Properties of cardiac conduction in a cell-based computational model
The conduction of electrical signals through cardiac tissue is essential for maintaining the function of the heart, and conduction abnormalities are known to potentially lead to life-threatening arrhythmias. The properties of cardiac conduction have therefore been the topic of intense study for decades, but a number of questions related to the mechanisms of conduction still remain unresolved. In this paper, we demonstrate how the so-called EMI model may be used to study some of these open questions. In the EMI model, the extracellular space, the cell membrane, the intracellular space and the cell connections are all represented as separate parts of the computational domain, and the model therefore allows for study of local properties that are hard to represent in the classical homogenized bidomain or monodomain models commonly used to study cardiac conduction. We conclude that a non-uniform sodium channel distribution increases the conduction velocity and decreases the time delays over gap junctions of reduced coupling in the EMI model simulations. We also present a theoretical optimal cell length with respect to conduction velocity and consider the possibility of ephaptic coupling (i.e. cell-to-cell coupling through the extracellular potential) acting as an alternative or supporting mechanism to gap junction coupling. We conclude that for a non-uniform distribution of sodium channels and a sufficiently small intercellular distance, ephaptic coupling can influence the dynamics of the sodium channels and potentially provide cell-to-cell coupling when the gap junction connection is absent.
Afilliation | Scientific Computing |
Project(s) | Department of Computational Physiology |
Publication Type | Journal Article |
Year of Publication | 2019 |
Journal | PLoS Computational Biology |
Volume | 15 |
Issue | 5 |
Number | e1007042 |
Date Published | 05/2019 |
Publisher | Public Library of Science |
URL | https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1... |
DOI | 10.1371/journal.pcbi.1007042 |
Talks, contributed
A one-dimensional computational study of mechano-electric feedback and arrhythmogenic current generation
In Gordon Research Conference "Cardiac Arrhythmia Mechanisms", Barga, Italy, 2019.Status: Published
A one-dimensional computational study of mechano-electric feedback and arrhythmogenic current generation
Afilliation | Scientific Computing |
Project(s) | Department of Computational Physiology |
Publication Type | Talks, contributed |
Year of Publication | 2019 |
Location of Talk | Gordon Research Conference "Cardiac Arrhythmia Mechanisms", Barga, Italy |
Talks, contributed
A computational study of the contribution of mechano-electric feedback to arrhythmogenic current generation
In Berlin, Germany. Heart by Numbers, Biophysical Society, 2018.Status: Published
A computational study of the contribution of mechano-electric feedback to arrhythmogenic current generation
Afilliation | Scientific Computing |
Project(s) | Department of Computational Physiology |
Publication Type | Talks, contributed |
Year of Publication | 2018 |
Location of Talk | Berlin, Germany |
Publisher | Heart by Numbers, Biophysical Society |
Journal Article
Computational Modeling of Electrophysiology and Pharmacotherapy of Atrial Fibrillation: Recent Advances and Future Challenges
Frontiers in Physiology 9 (2018): 1221.Status: Published
Computational Modeling of Electrophysiology and Pharmacotherapy of Atrial Fibrillation: Recent Advances and Future Challenges
Afilliation | Scientific Computing |
Project(s) | AFib-TrainNet: EU Training Network on Novel Targets and Methods in Atrial Fibrillation |
Publication Type | Journal Article |
Year of Publication | 2018 |
Journal | Frontiers in Physiology |
Volume | 9 |
Pagination | 1221 |
Date Published | Apr-09-2018 |
Publisher | Frontiers in Physiology |
URL | https://www.frontiersin.org/article/10.3389/fphys.2018.01221/fullhttps:/... |
DOI | 10.3389/fphys.2018.01221 |
Inversion and computational maturation of drug response using human stem cell derived cardiomyocytes in microphysiological systems
Nature Scientific Reports 8 (2018).Status: Published
Inversion and computational maturation of drug response using human stem cell derived cardiomyocytes in microphysiological systems
While cardiomyocytes differentiated from human induced pluripotent stems cells (hiPSCs) hold great promise for drug screening, the electrophysiological properties of these cells can be variable and immature, producing results that are significantly different from their human adult counterparts. Here, we describe a computational framework to address this limitation, and show how in silico methods, applied to measurements on immature cardiomyocytes, can be used to both identify drug action and to predict its effect in mature cells. Our synthetic and experimental results indicate that optically obtained waveforms of voltage and calcium from microphysiological systems can be inverted into information on drug ion channel blockage, and then, through assuming functional invariance of proteins during maturation, this data can be used to predict drug induced changes in mature ventricular cells. Together, this pipeline of measurements and computational analysis could significantly improve the ability of hiPSC derived cardiomycocytes to predict dangerous drug side effects.
Afilliation | Scientific Computing |
Project(s) | Center for Biomedical Computing (SFF) |
Publication Type | Journal Article |
Year of Publication | 2018 |
Journal | Nature Scientific Reports |
Volume | 8 |
Number | 17626 |
Date Published | 12/2018 |
Publisher | Springer Nature |
URL | https://doi.org/10.1038/s41598-018-35858-7 |
DOI | 10.1038/s41598-018-35858-7 |
Ryanodine Receptor Dispersion Disrupts Ca2+-Release in Failing Cardiac Myocytes
eLife 7 (2018): e39427.Status: Published
Ryanodine Receptor Dispersion Disrupts Ca2+-Release in Failing Cardiac Myocytes
Afilliation | Scientific Computing |
Project(s) | No Simula project |
Publication Type | Journal Article |
Year of Publication | 2018 |
Journal | eLife |
Volume | 7 |
Pagination | e39427 |
Date Published | 10/2018 |
Publisher | eLife Sciences Publications |
ISSN | 2050-084X |
URL | https://elifesciences.org/articles/39427 |
DOI | 10.7554/eLife.39427 |
Journal Article
An Evaluation of the Accuracy of Classical Models for Computing the Membrane Potential and Extracellular Potential for Neurons
Frontiers in Computational Neuroscience 11 (2017): 27.Status: Published
An Evaluation of the Accuracy of Classical Models for Computing the Membrane Potential and Extracellular Potential for Neurons
Two mathematical models are part of the foundation of Computational neurophysiology; a) the Cable equation is used to compute the membrane potential of neurons, and, b) volume-conductor theory describes the extracellular potential around neurons. In the standard procedure for computing extracellular potentials, the transmembrane currents are computed by means of a) and the extracellular potentials are computed using an explicit sum over analytical point-current source solutions as prescribed by volume conductor theory. Both models are extremely useful as they allow huge simplifications of the computational efforts involved in computing extracellular potentials. However, there are more accurate, though
computationally very expensive, models available where the potentials inside and outside the neurons are computed simultaneously in a self-consistent scheme. In the present work we explore the accuracy of the classical models a) and b) by comparing them to these more accurate schemes.
The main assumption of a) is that the ephaptic current can be ignored in the derivation of the Cable equation. We find, however, for our examples with stylized neurons, that the ephaptic current is comparable in magnitude to other currents involved in the computations, suggesting that it may be significant – at least in parts of the simulation. The magnitude of the error introduced in the membrane potential is several millivolts, and this error also translates into errors in the predicted extracellular potentials. While the error becomes negligible if we assume the extracellular conductivity to be very large, this assumption is, unfortunately, not easy to justify a priori for all situations of interest.
Afilliation | Scientific Computing |
Project(s) | Center for Biomedical Computing (SFF) |
Publication Type | Journal Article |
Year of Publication | 2017 |
Journal | Frontiers in Computational Neuroscience |
Volume | 11 |
Pagination | 27 |
Publisher | Frontiers Media SA |
ISSN | 1662-5188 |
URL | http://journal.frontiersin.org/article/10.3389/fncom.2017.00027 |
DOI | 10.3389/fncom.2017.00027 |
An integrative appraisal of mechano-electric feedback mechanisms in the heart
Progress in biophysics and molecular biology 130 (2017): 404-417.Status: Published
An integrative appraisal of mechano-electric feedback mechanisms in the heart
Afilliation | Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2017 |
Journal | Progress in biophysics and molecular biology |
Volume | 130 |
Pagination | 404–417 |
Publisher | Elsevier |
Pleiotropic effects of schizophrenia-associated genetic variants in neuron firing and cardiac pacemaking revealed by computational modeling
Translational Psychiatry 7 (2017): 5.Status: Published
Pleiotropic effects of schizophrenia-associated genetic variants in neuron firing and cardiac pacemaking revealed by computational modeling
Afilliation | Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2017 |
Journal | Translational Psychiatry |
Volume | 7 |
Number | 11 |
Pagination | 5 |
Publisher | Nature Publishing Group |
Species-Dependent Mechanisms of Cardiac Arrhythmia: A Cellular Focus
Clinical Medicine Insights: Cardiology 11 (2017).Status: Published
Species-Dependent Mechanisms of Cardiac Arrhythmia: A Cellular Focus
Afilliation | Scientific Computing |
Project(s) | Center for Biomedical Computing (SFF) |
Publication Type | Journal Article |
Year of Publication | 2017 |
Journal | Clinical Medicine Insights: Cardiology |
Volume | 11 |
Publisher | SAGE Publications |
ISSN | 1179-5468 |
DOI | 10.1177/1179546816686061 |
Studying dyadic structure-function relationships: a review of current modeling approaches and new insights into Ca2+ (mis)handling
Clinical Medicine Insights: Cardiology 11 (2017): 1-11.Status: Published
Studying dyadic structure-function relationships: a review of current modeling approaches and new insights into Ca2+ (mis)handling
Afilliation | Scientific Computing |
Project(s) | Center for Biomedical Computing (SFF) |
Publication Type | Journal Article |
Year of Publication | 2017 |
Journal | Clinical Medicine Insights: Cardiology |
Volume | 11 |
Pagination | 1-11 |
Date Published | 04/2017 |
Publisher | Libertas Academica |
URL | http://insights.sagepub.com/studying-dyadic-structurefunction-relationsh... |
DOI | 10.1177/1179546817698602 |
Talks, contributed
Integrated Mechanisms of Mechano-Electric feedback in Ischemic Arrhythmogenesis
In Bergen, Norway, 2017.Status: Published
Integrated Mechanisms of Mechano-Electric feedback in Ischemic Arrhythmogenesis
Afilliation | Scientific Computing |
Publication Type | Talks, contributed |
Year of Publication | 2017 |
Location of Talk | Bergen, Norway |
Poster
Integrated Mechanisms of Mechano-Electric Feedback in Ischemic Arrhythmogenesis
Oslo, Norway, 2017.Status: Published
Integrated Mechanisms of Mechano-Electric Feedback in Ischemic Arrhythmogenesis
Afilliation | Scientific Computing |
Publication Type | Poster |
Year of Publication | 2017 |
Date Published | 09/2017 |
Place Published | Oslo, Norway |
Role of Electromechanical Feedback in Stretch Induced Arrhythmias : From Single Myocyte to Multicellular Level
Gordon Research Conference on Arrhythmia Mechanisms, Ventura, California, USA, 2017.Status: Published
Role of Electromechanical Feedback in Stretch Induced Arrhythmias : From Single Myocyte to Multicellular Level
Afilliation | Scientific Computing |
Project(s) | No Simula project |
Publication Type | Poster |
Year of Publication | 2017 |
Date Published | 02/2017 |
Place Published | Gordon Research Conference on Arrhythmia Mechanisms, Ventura, California, USA |
Journal Article
Atrial-selective targeting of arrhythmogenic phase-3 early afterdepolarizations in human myocytes
Journal of Molecular and Cellular Cardiology 96 (2016): 63-71.Status: Published
Atrial-selective targeting of arrhythmogenic phase-3 early afterdepolarizations in human myocytes
Afilliation | Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2016 |
Journal | Journal of Molecular and Cellular Cardiology |
Volume | 96 |
Pagination | 63-71 |
Publisher | Academic Press |
Computing rates of Markov models of voltage-gated ion channels by inverting partial differential equations governing the probability density functions of the conducting and non-conducting states
Mathematical Biosciences 277 (2016): 126-135.Status: Published
Computing rates of Markov models of voltage-gated ion channels by inverting partial differential equations governing the probability density functions of the conducting and non-conducting states
Afilliation | Scientific Computing |
Project(s) | Center for Biomedical Computing (SFF) |
Publication Type | Journal Article |
Year of Publication | 2016 |
Journal | Mathematical Biosciences |
Volume | 277 |
Pagination | 126-135 |
Publisher | Elsevier Inc |
Book Chapter
Calcium Signaling in Cardiomyocyte Models With Realistic Geometries (7th Edition)
In Cardiac Electrophysiology: From Cell to Bedside. 7th ed. Elsevier Science, 2016.Status: Accepted
Calcium Signaling in Cardiomyocyte Models With Realistic Geometries (7th Edition)
Afilliation | Scientific Computing, , Scientific Computing |
Project(s) | Center for Biomedical Computing (SFF) |
Publication Type | Book Chapter |
Year of Publication | 2016 |
Book Title | Cardiac Electrophysiology: From Cell to Bedside |
Edition | 7 |
Chapter | 33 |
Publisher | Elsevier Science |
ISBN Number | 9781455728565 |
Poster
Role of Electromechanical Feedback in Mitral Valve Prolapse Arrhythmia
Freiburg, Germany: Conference on Cardiac Mechano-Electric Couping and Arrhythmias, 2016.Status: Published
Role of Electromechanical Feedback in Mitral Valve Prolapse Arrhythmia
Afilliation | Scientific Computing |
Publication Type | Poster |
Year of Publication | 2016 |
Date Published | 09/2016 |
Publisher | Conference on Cardiac Mechano-Electric Couping and Arrhythmias |
Place Published | Freiburg, Germany |
Journal Article
Atrial-selective targeting of arrhythmogenic phase-3 early afterdepolarizations in human myocytes
Journal of Molecular and Cellular Cardiology In Press (2015).Status: Published
Atrial-selective targeting of arrhythmogenic phase-3 early afterdepolarizations in human myocytes
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2015 |
Journal | Journal of Molecular and Cellular Cardiology |
Volume | In Press |
Publisher | Academic Press |
Na+/Ca2+ exchange and Na+/K+-ATPase in the heart
The Journal of Physiology 593, no. 6 (2015): 1361-1382.Status: Published
Na+/Ca2+ exchange and Na+/K+-ATPase in the heart
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2015 |
Journal | The Journal of Physiology |
Volume | 593 |
Issue | 6 |
Pagination | 1361-1382 |
Publisher | John Wiley & Sons |
Poster
Ranolazine Prevents Phase-3 Early Afterdepolarizations in Human Atrial Myocytes by Inhibiting Na Current Non-Equilibrium Reactivation
In Biophysical Society annual meeting. Elsevier, 2015.Status: Published
Ranolazine Prevents Phase-3 Early Afterdepolarizations in Human Atrial Myocytes by Inhibiting Na Current Non-Equilibrium Reactivation
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Poster |
Year of Publication | 2015 |
Secondary Title | Biophysical Society annual meeting |
Date Published | 01/27/2015 |
Publisher | Elsevier |
Secretoneurin, a Novel Endogenous CaMKII Inhibitor, Augments Cardiomyocyte Calcium Handling and Inhibits Arrhythmogenic Calcium Release
In Biophysical Journal. Vol. 108. Elsevier, 2015.Status: Published
Secretoneurin, a Novel Endogenous CaMKII Inhibitor, Augments Cardiomyocyte Calcium Handling and Inhibits Arrhythmogenic Calcium Release
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Poster |
Year of Publication | 2015 |
Secondary Title | Biophysical Journal |
Publisher | Elsevier |
Proceedings, non-refereed
A Markov-State Model for the Regulation of the Sarcoplasmic Reticulum Ca2+ ATPase by Phospholamban
In Annual meeting in Biophysical society. Vol. 106. Elsevier, 2014.Status: Published
A Markov-State Model for the Regulation of the Sarcoplasmic Reticulum Ca2+ ATPase by Phospholamban
Compelling evidence suggests that reduced sarcoplasmic reticulum (SR) Ca 2+ uptake via
the SR Ca 2+ ATPase (SERCA) is a major contributor to the development of Ca 2+ signaling
abnormalities in heart failure, and equally important as other known contributors to impaired
Ca 2+ handling.
Afilliation | Scientific Computing, , Scientific Computing |
Project(s) | Center for Biomedical Computing (SFF) |
Publication Type | Proceedings, non-refereed |
Year of Publication | 2014 |
Conference Name | Annual meeting in Biophysical society |
Volume | 106 |
Date Published | 01/2014 |
Publisher | Elsevier |
Journal Article
A novel computational model of mouse myocyte electrophysiology to assess the synergy between Na+ loading and CaMKII
The Journal of physiology 592, no. 6 (2014): 1181-1197.Status: Published
A novel computational model of mouse myocyte electrophysiology to assess the synergy between Na+ loading and CaMKII
Afilliation | Scientific Computing, , Scientific Computing |
Project(s) | Center for Biomedical Computing (SFF) |
Publication Type | Journal Article |
Year of Publication | 2014 |
Journal | The Journal of physiology |
Volume | 592 |
Issue | 6 |
Pagination | 1181-1197 |
Date Published | 03/2014 |
Publisher | Wiley-Blackwell |
A novel computational model of mouse myocyte electrophysiology to assess the synergy between Na+ loading and CaMKII
The Journal of Physiology 592, no. 6 (2014): 1181-1197.Status: Published
A novel computational model of mouse myocyte electrophysiology to assess the synergy between Na+ loading and CaMKII
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2014 |
Journal | The Journal of Physiology |
Volume | 592 |
Issue | 6 |
Pagination | 1181-1197 |
Publisher | John Wiley & Sons |
CaMKII comes of age in cardiac health and disease
Frontiers in Pharmacology 5 (2014).Status: Published
CaMKII comes of age in cardiac health and disease
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2014 |
Journal | Frontiers in Pharmacology |
Volume | 5 |
Publisher | Frontiers Media SA |
CaMKII comes of age in cardiac health and disease.
Frontiers in pharmacology (2014).Status: Published
CaMKII comes of age in cardiac health and disease.
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2014 |
Journal | Frontiers in pharmacology |
Publisher | Frontiers Media S.A. |
Caveolae in ventricular myocytes are required for stretch-dependent conduction slowing
Journal of Molecular and Cellular Cardiology 76 (2014): 265-274.Status: Published
Caveolae in ventricular myocytes are required for stretch-dependent conduction slowing
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2014 |
Journal | Journal of Molecular and Cellular Cardiology |
Volume | 76 |
Pagination | 265-274 |
Publisher | Academic Press |
Non-equilibrium reactivation of Na+ current drives early afterdepolarizations in mouse ventricle
Circulation: Arrhythmia and Electrophysiology 7, no. 6 (2014): 1205-1213.Status: Published
Non-equilibrium reactivation of Na+ current drives early afterdepolarizations in mouse ventricle
Afilliation | Scientific Computing |
Project(s) | Center for Biomedical Computing (SFF) |
Publication Type | Journal Article |
Year of Publication | 2014 |
Journal | Circulation: Arrhythmia and Electrophysiology |
Volume | 7 |
Issue | 6 |
Pagination | 1205-1213 |
Publisher | Lippincott Williams & Wilkins (United States) |
Place Published | Worldwide |
Toward a hierarchy of mechanisms in CaMKII-mediated arrhythmia
Frontiers in Pharmacology 5 (2014).Status: Published
Toward a hierarchy of mechanisms in CaMKII-mediated arrhythmia
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2014 |
Journal | Frontiers in Pharmacology |
Volume | 5 |
Publisher | Frontiers Media SA |
Toward a hierarchy of mechanisms in CaMKII-mediated arrhythmia
Frontiers in Pharmacology 5, no. 110 (2014).Status: Published
Toward a hierarchy of mechanisms in CaMKII-mediated arrhythmia
Afilliation | Scientific Computing, , Scientific Computing |
Project(s) | Center for Biomedical Computing (SFF) |
Publication Type | Journal Article |
Year of Publication | 2014 |
Journal | Frontiers in Pharmacology |
Volume | 5 |
Issue | 110 |
Publisher | Frontiers Media S.A. |
Book Chapter
Calcium Signaling in Cardiomyocyte Models With Realistic Geometries (6th Edition)
In Cardiac Electrophysiology: From Cell to Bedside , 33.1-33.10. 6th ed. Elsevier Science, 2013.Status: Published
Calcium Signaling in Cardiomyocyte Models With Realistic Geometries (6th Edition)
Afilliation | Scientific Computing, Scientific Computing, , Scientific Computing |
Project(s) | Center for Biomedical Computing (SFF) |
Publication Type | Book Chapter |
Year of Publication | 2013 |
Book Title | Cardiac Electrophysiology: From Cell to Bedside |
Edition | 6 |
Chapter | 33 |
Pagination | 33.1-33.10 |
Date Published | 2013 |
Publisher | Elsevier Science |
ISBN Number | 9781455728565 |
Journal Article
Conference report from the 2012 AHA scientific sessions in Los Angeles
Expert Opinion on Therapeutic Targets 17, no. 6 (2013): 733-737.Status: Published
Conference report from the 2012 AHA scientific sessions in Los Angeles
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2013 |
Journal | Expert Opinion on Therapeutic Targets |
Volume | 17 |
Issue | 6 |
Pagination | 733-737 |
Publisher | Informa UK, Ltd. London |
The promise of CaMKII inhibition for heart disease: preventing heart failure and arrhythmias
Expert opinion on therapeutic targets 17, no. 8 (2013): 889-993.Status: Published
The promise of CaMKII inhibition for heart disease: preventing heart failure and arrhythmias
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2013 |
Journal | Expert opinion on therapeutic targets |
Volume | 17 |
Issue | 8 |
Pagination | 889-993 |
Publisher | Informa UK, Ltd. London |
Journal Article
Instabilities of the Resting State in a Mathematical Model of Calcium Handling in Cardiac Myocytes
Mathematical Biosciences 236 (2012): 97-107.Status: Published
Instabilities of the Resting State in a Mathematical Model of Calcium Handling in Cardiac Myocytes
Afilliation | Scientific Computing |
Project(s) | Center for Biomedical Computing (SFF) |
Publication Type | Journal Article |
Year of Publication | 2012 |
Journal | Mathematical Biosciences |
Volume | 236 |
Number | 2 |
Pagination | 97-107 |
Publisher | Elsevier |
DOI | 10.1016/j.mbs.2012.02.005 |
Modeling Cardiac Calcium Sparks in a Three-Dimensional Reconstruction of a Calcium Release Unit
The Journal of Physiology 590 (2012): 4403-4422.Status: Published
Modeling Cardiac Calcium Sparks in a Three-Dimensional Reconstruction of a Calcium Release Unit
Afilliation | Scientific Computing, , Scientific Computing, Scientific Computing |
Project(s) | Center for Biomedical Computing (SFF) |
Publication Type | Journal Article |
Year of Publication | 2012 |
Journal | The Journal of Physiology |
Volume | 590 |
Number | 18 |
Pagination | 4403-4422 |
Date Published | Sept |
Slow Calcium-Depolarization-Calcium Waves May Initiate Fast Local Depolarization Waves in Ventricular Tissue
Progress in Biophysics and Molecular Biology 110 (2012): 295-304.Status: Published
Slow Calcium-Depolarization-Calcium Waves May Initiate Fast Local Depolarization Waves in Ventricular Tissue
Intercellular calcium waves in cardiac myocytes are a well-recognized, if incompletely understood, phenomenon. In a variety of preparations, investigators have reported multi-cellular calcium waves or triggered propagated contractions, but the mechanisms of propagation and pathological importance of these events remain unclear. Here, we review existing experimental data and present a computational approach to investigate the mechanisms of multi-cellular calcium wave propagation. Over the past 50 years, the standard modeling paradigm for excitable cardiac tissue has seen increasingly detailed models of the dynamics of individual cells coupled in tissue solely by intercellular and interstitial current flow. Although very successful, this modeling regime has been unable to capture two important phenomena: 1) the slow intercellular calcium waves observed experimentally, and 2) how intercellular calcium events resulting in delayed after depolarizations at the cellular level could overcome a source-sink mismatch to initiate depolarization waves in tissue. In this paper, we introduce a mathematical model with subcellular spatial resolution, in which we allow both inter- and intracellular current flow and calcium diffusion. In simulations of coupled cells employing this model, we observe: a) slow inter-cellular calcium waves propagating at about 0.1 mm/s, b) faster Calcium-Depolarization-Calcium (CDC) waves, traveling at about 1 mm/s, and c) CDC- waves that can set off fast depolarization-waves (50 cm/s) in tissue with varying gap-junction conductivity.
Afilliation | Scientific Computing, , Scientific Computing, Scientific Computing |
Project(s) | Center for Biomedical Computing (SFF) |
Publication Type | Journal Article |
Year of Publication | 2012 |
Journal | Progress in Biophysics and Molecular Biology |
Volume | 110 |
Number | 2-3 |
Pagination | 295-304 |
Date Published | July 24 |
Poster
Modeling Calcium Sparks in a Three-Dimensional Reconstruction of a Cardiac Calcium Release Unit
2012.Status: Published
Modeling Calcium Sparks in a Three-Dimensional Reconstruction of a Cardiac Calcium Release Unit
Afilliation | Scientific Computing, , Scientific Computing, Scientific Computing |
Project(s) | Center for Biomedical Computing (SFF) |
Publication Type | Poster |
Year of Publication | 2012 |
βAR-Stimulation Causes EADs But Not DADs in Pre-Failure CAMKIIδC Transgenic Myocytes
In Biophysical Society annual meeting, 2012.Status: Published
βAR-Stimulation Causes EADs But Not DADs in Pre-Failure CAMKIIδC Transgenic Myocytes
Afilliation | Scientific Computing, Scientific Computing, , Scientific Computing |
Project(s) | Center for Biomedical Computing (SFF) |
Publication Type | Poster |
Year of Publication | 2012 |
Secondary Title | Biophysical Society annual meeting |
Journal Article
Measuring changes in aerodynamic/rolling resistances by cycle-mounted power meters
Medicine and science in sports and exercise 43, no. 5 (2011): 853-860.Status: Published
Measuring changes in aerodynamic/rolling resistances by cycle-mounted power meters
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2011 |
Journal | Medicine and science in sports and exercise |
Volume | 43 |
Issue | 5 |
Pagination | 853-860 |
Publisher | Wolters Kluwer |
What for nature, and who to nurture?
Journal of Applied Physiology 110, no. 1 (2011).Status: Published
What for nature, and who to nurture?
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2011 |
Journal | Journal of Applied Physiology |
Volume | 110 |
Issue | 1 |
Publisher | American Physiological Society |
What for nature, and who to nurture?
Journal of Applied Physiology 110, no. 1 (2011).Status: Published
What for nature, and who to nurture?
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2011 |
Journal | Journal of Applied Physiology |
Volume | 110 |
Issue | 1 |
Publisher | American Physiological Society |
Journal Article
Accuracy of optimized branched algorithms to assess activity-specific PAEE
Medicine and science in sports and exercise 42, no. 4 (2010): 672.Status: Published
Accuracy of optimized branched algorithms to assess activity-specific PAEE
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2010 |
Journal | Medicine and science in sports and exercise |
Volume | 42 |
Issue | 4 |
Pagination | 672 |
Publisher | NIH Public Access |
Life-long caloric restriction elicits pronounced protection of the aged myocardium: a role for AMPK
Mechanisms of ageing and development 131, no. 11 (2010): 739-742.Status: Published
Life-long caloric restriction elicits pronounced protection of the aged myocardium: a role for AMPK
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2010 |
Journal | Mechanisms of ageing and development |
Volume | 131 |
Issue | 11 |
Pagination | 739-742 |
Publisher | Elsevier |
Life-long caloric restriction elicits pronounced protection of the aged myocardium: a role for AMPK
Mechanisms of Aging and Development 131, no. 11 (2010): 739-742.Status: Published
Life-long caloric restriction elicits pronounced protection of the aged myocardium: a role for AMPK
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2010 |
Journal | Mechanisms of Aging and Development |
Volume | 131 |
Issue | 11 |
Pagination | 739-742 |
Publisher | Elsevier |
Journal Article
PKC-permitted elevation of sarcolemmal KATP concentration may explain female-specific resistance to myocardial infarction
The Journal of Physiology 587, no. 23 (2009): 5723-5737.Status: Published
PKC-permitted elevation of sarcolemmal KATP concentration may explain female-specific resistance to myocardial infarction
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2009 |
Journal | The Journal of Physiology |
Volume | 587 |
Issue | 23 |
Pagination | 5723-5737 |
Publisher | Blackwell Publishing Ltd |
Journal Article
Aerodynamic characteristics as determinants of the drafting effect in cycling.
Medicine and science in sports and exercise 39, no. 1 (2007): 170-176.Status: Published
Aerodynamic characteristics as determinants of the drafting effect in cycling.
Afilliation | Scientific Computing, Scientific Computing |
Publication Type | Journal Article |
Year of Publication | 2007 |
Journal | Medicine and science in sports and exercise |
Volume | 39 |
Issue | 1 |
Pagination | 170-176 |
Publisher | Wolters Kluwer |