@article {42456,
	title = {Arrhythmogenic influence of mutations in a myocyte-based computational model of the pulmonary vein sleeve},
	journal = {Nature Scientific Reports },
	volume = {12},
	year = {2022},
	pages = {7040},
	publisher = {Springer Nature},
	abstract = {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{\textquoteright}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{\textquoteright}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.},
	doi = {https://doi.org/10.1038/s41598-022-11110-1},
	url = {https://rdcu.be/cMntU},
	author = {Karoline Horgmo {J{\ae}ger} and Andrew G {Edwards} and Wayne R. {Giles} and Tveito, Aslak}
}
@article {42946,
	title = {Image-Driven Modeling of Nanoscopic Cardiac Function: Where Have We Come From, and Where Are We Going?},
	journal = {Frontiers in Physiology},
	volume = {13},
	year = {2022},
	month = {Aug-03-2022},
	publisher = {Frontiers},
	doi = {10.3389/fphys.2022.834211},
	url = {https://www.frontiersin.org/articles/10.3389/fphys.2022.834211/fullhttps://www.frontiersin.org/articles/10.3389/fphys.2022.834211/full},
	author = {William E. {Louch} and Perdreau-Dahl, Harmonie and Andrew G {Edwards}}
}
@article {42947,
	title = {Mechanisms of spontaneous Ca 2+               release-mediated arrhythmia in a novel 3D human atrial myocyte model: I. Transverse-axial tubule variation},
	journal = {The Journal of Physiology},
	year = {2022},
	publisher = {The Physiological Society},
	issn = {0022-3751},
	doi = {10.1113/JP283363},
	url = {https://onlinelibrary.wiley.com/doi/10.1113/JP283363https://onlinelibrary.wiley.com/doi/pdf/10.1113/JP283363https://onlinelibrary.wiley.com/doi/pdf/10.1113/JP283363https://onlinelibrary.wiley.com/doi/full-xml/10.1113/JP283363},
	author = {Zhang, Xianwei and Ni, Haibo and Morotti, Stefano and Charlotte E. R. {Smith} and Sato, Daisuke and William E. {Louch} and Andrew G {Edwards} and Grandi, Eleonora}
}
@article {42949,
	title = {Mechanisms of spontaneous Ca2+ release-mediated arrhythmia in a novel 3D human atrial myocyte model: II Ca2+-handling protein variation},
	journal = {The Journal of Physiology},
	volume = {116},
	year = {2022},
	publisher = {The Physiological Society},
	issn = {0022-3751},
	doi = {10.1113/JP283602},
	url = {https://onlinelibrary.wiley.com/doi/10.1113/JP283602https://onlinelibrary.wiley.com/doi/pdf/10.1113/JP283602https://onlinelibrary.wiley.com/doi/pdf/10.1113/JP283602https://onlinelibrary.wiley.com/doi/full-xml/10.1113/JP283602},
	author = {Zhang, Xianwei and Charlotte E. R. {Smith} and Morotti, Stefano and Andrew G {Edwards} and Sato, Daisuke and William E. {Louch} and Ni, Haibo and Grandi, Eleonora}
}
@article {42717,
	title = {Metabolically driven maturation of human-induced-pluripotent-stem-cell-derived cardiac microtissues on microfluidic chips},
	journal = {Nature Biomedical Engineering},
	volume = {6},
	year = {2022},
	month = {Jan-04-2022},
	pages = {372 - 388},
	publisher = {Nature Publishing Group},
	address = {London, UK},
	doi = {10.1038/s41551-022-00884-4},
	url = {https://www.nature.com/articles/s41551-022-00884-4https://www.nature.com/articles/s41551-022-00884-4.pdfhttps://www.nature.com/articles/s41551-022-00884-4.pdfhttps://www.nature.com/articles/s41551-022-00884-4},
	author = {Huebsch, Nathaniel and Charrez, Berenice and Neiman, Gabriel and Siemons, Brian and Steven C. {Boggess} and Wall, Samuel and Charwat, Verena and Karoline Horgmo {J{\ae}ger} and Cleres, David and Telle, {\r A}shild and Felipe T. {Lee-Montiel} and Nicholas C. {Jeffreys} and Deveshwar, Nikhil and Andrew G {Edwards} and Serrano, Jonathan and Snuderl, Matija and Stahl, Andreas and Tveito, Aslak and Evan W. {Miller} and Kevin E. {Healy}}
}
@article {42622,
	title = {Prolonged β-adrenergic stimulation disperses ryanodine receptor clusters in cardiomyocytes},
	journal = {eLife},
	volume = {11},
	year = {2022},
	month = {Jan-08-2022},
	publisher = {eLife},
	address = {eLife},
	abstract = {Ryanodine Receptors (RyRs) exhibit dynamic arrangements in cardiomyocytes, and we previously showed that {\textquoteright}dispersion{\textquoteright} of RyR clusters disrupts Ca2+\&nbsp;homeostasis during heart failure (HF) (Kolstad\&nbsp;et al., eLife, 2018). Here, we investigated whether prolonged β-adrenergic stimulation, a hallmark of HF, promotes RyR cluster dispersion, and examined the underlying mechanisms. We observed that treatment of healthy rat cardiomyocytes with isoproterenol for 1 hour triggered progressive fragmentation of RyR clusters. Pharmacological inhibition of CaMKII reversed these effects, while cluster dispersion was reproduced by specific activation of CaMKII, and in mice with constitutively active Ser2814-RyR. A similar role of protein kinase A (PKA) in promoting RyR cluster fragmentation was established by employing PKA activation or inhibition. Progressive cluster dispersion was linked to declining Ca2+\&nbsp;spark fidelity and magnitude, and slowed release kinetics from Ca2+\&nbsp;propagation between more numerous RyR clusters. In healthy cells, this served to dampen the stimulatory actions of β-adrenergic stimulation over the longer term, and protect against pro-arrhythmic Ca2+\&nbsp;waves. However, during HF, RyR dispersion was linked to impaired Ca2+\&nbsp;release. Thus, RyR localization and function are intimately linked via channel phosphorylation by both CaMKII and PKA which, while finely tuned in healthy cardiomyocytes, underlies impaired cardiac function during pathology.ADD A COMMENT\&nbsp;+Open annotations. The current annotation count on this page is\&nbsp;0.Data availability},
	doi = {10.7554/eLife.77725},
	url = {https://elifesciences.org/articles/77725https://cdn.elifesciences.org/articles/77725/elife-77725-v1.pdfhttps://cdn.elifesciences.org/articles/77725/elife-77725-v1.xml},
	author = {Shen, Xin and van den Brink, Jonas and Bergan-Dahl, Anna and Terje R {Kolstad} and Einar Sjaastad {Norden} and Hou, Yufeng and Laasmaa, Martin and Aguilar-Sanchez, Yuriana and Ann Pepper {Quick} and Emil Knut Stene {Espe} and Sjaastad, Ivar and Xander HT {Wehrens} and Andrew G {Edwards} and Soeller, Christian and William Edward {Louch}}
}
@article {43086,
	title = {Validating the Arrhythmogenic Potential of High-, Intermediate-, and Low-Risk Drugs in a Human-Induced Pluripotent Stem Cell-Derived Cardiac Microphysiological System},
	journal = {ACS Pharmacology \& Translational Science},
	volume = {5},
	year = {2022},
	pages = {652{\textendash}667},
	publisher = {American Chemical Society},
	abstract = {Evaluation of arrhythmogenic drugs is required by regulatory agencies before any new compound can obtain market approval. Despite rigorous review, cardiac disorders remain the second most common cause for safety-related market withdrawal. On the other hand, false-positive preclinical findings prohibit potentially beneficial candidates from moving forward in the development pipeline. Complex\&nbsp;in vitro\&nbsp;models using cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CM) have been identified as a useful tool that allows for rapid and cost-efficient screening of proarrhythmic drug risk. Currently available hiPSC-CM models employ simple two-dimensional (2D) culture formats with limited structural and functional relevance to the human heart muscle. Here, we present the use of our 3D cardiac microphysiological system (MPS), composed of a hiPSC-derived heart micromuscle, as a platform for arrhythmia risk assessment. We employed two different hiPSC lines and tested seven drugs with known ion channel effects and known clinical risk: dofetilide and bepridil (high risk); amiodarone and terfenadine (intermediate risk); and nifedipine, mexiletine, and lidocaine (low risk). The cardiac MPS successfully predicted drug cardiotoxicity risks based on changes in action potential duration, beat waveform (i.e., shape), and occurrence of proarrhythmic events of healthy patient hiPSC lines in the absence of risk cofactors. We showcase examples where the cardiac MPS outperformed existing hiPSC-CM 2D models.},
	doi = {https://doi.org/10.1021/acsptsci.2c00088},
	url = {https://pubs.acs.org/doi/abs/10.1021/acsptsci.2c00088},
	author = {Charwat, Verena and Charrez, B{\'e}r{\'e}nice and Brian A. {Siemons} and Finsberg, Henrik and Karoline Horgmo {J{\ae}ger} and Andrew G {Edwards} and Huebsch, Nathaniel and Wall, Samuel and Miller, Evan and Tveito, Aslak and Kevin E. {Healy}}
}
@inbook {28434,
	title = {Calcium Signaling in Cardiomyocyte Models With Realistic Geometries},
	booktitle = {Zipes and Jalife{\textquoteright}s Cardiac Electrophysiology: From Cell to Bedside},
	volume = {1},
	year = {2021},
	month = {12/2021},
	pages = {362-375},
	publisher = { Elsevier},
	organization = { Elsevier},
	edition = {8},
	chapter = {32},
	author = {Andrew G {Edwards} and van den Brink, Jonas and Andrew D. {McCulloch}},
	editor = {Jalife, Jose and William G {Stevenson}}
}
@article {27937,
	title = {A computational method for identifying an optimal combination of existing drugs to repair the action potentials of SQT1 ventricular myocytes},
	journal = {PLoS Computational Biology},
	volume = {17},
	number = {8},
	year = {2021},
	pages = {e1009233},
	publisher = {Public Library of Science},
	abstract = {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 {\textquoteleft}repair{\textquoteright} 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 {\textquoteleft}composition{\textquoteright} 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.},
	doi = {https://doi. org/10.1371/journal.pcbi.1009233},
	author = {Karoline Horgmo {J{\ae}ger} and Andrew G {Edwards} and Wayne R. {Giles} and Tveito, Aslak}
}
@article {28097,
	title = {From Millimeters to Micrometers; Re-introducing Myocytes in Models of Cardiac Electrophysiology},
	journal = {Frontiers in Physiology},
	volume = {12},
	year = {2021},
	pages = {763584},
	publisher = {Frontiers},
	abstract = {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\&nbsp;in silico\&nbsp;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.},
	doi = {https://doi.org/10.3389/fphys.2021.763584},
	url = {https://www.frontiersin.org/articles/10.3389/fphys.2021.763584/full},
	author = {Karoline Horgmo {J{\ae}ger} and Andrew G {Edwards} and Wayne R. {Giles} and Tveito, Aslak}
}
@article {27952,
	title = {Heart Muscle Microphysiological System for Cardiac Liability Prediction of Repurposed COVID-19 Therapeutics},
	journal = {Frontiers in Pharmacology},
	volume = {12},
	year = {2021},
	pages = {684252},
	publisher = {Frontiers Media SA},
	doi = {10.3389/fphar.2021.684252},
	url = {doi.org/10.3389/fphar.2021.684252},
	author = {Charrez, B{\'e}r{\'e}nice and Charwat, Verena and Siemons, Brian and Goswami, Ishan and Sakolish, Courtney and Luo, Yu-Syuan and Finsberg, Henrik and Andrew G {Edwards} and Miller, Evan and Rusyn, Ivan and Healy, Kevin}
}
@article {27951,
	title = {In vitro safety {\textquotedblleft}clinical trial{\textquotedblright} of the cardiac liability of drug polytherapy},
	journal = {Clinical and Translational Science},
	volume = {14},
	year = {2021},
	month = {03/2021},
	pages = {1155-1165},
	publisher = {Wiley Online Library},
	doi = {https://doi.org/10.1111/cts.13038},
	url = {https://ascpt.onlinelibrary.wiley.com/doi/full/10.1111/cts.13038},
	author = {Charrez, B{\'e}r{\'e}nice and Charwat, Verena and Siemons, Brian and Finsberg, Henrik and Miller, Evan and Andrew G {Edwards} and Kevin E. {Healy}}
}
@article {28303,
	title = {Sarcoplasmic Reticulum Calcium Release Is Required for Arrhythmogenesis in the MouseData_Sheet_1.pdf},
	journal = {Frontiers in Physiology},
	volume = {129247113307196118101757330290951073619410426311810310255549995881112965921565931388107972921061031069987209102119109419102782},
	year = {2021},
	month = {Dec-10-2021},
	publisher = {Frontiers},
	doi = {10.3389/fphys.2021.74473010.3389/fphys.2021.744730.s001},
	url = {https://www.frontiersin.org/articles/10.3389/fphys.2021.744730/fullhttps://www.frontiersin.org/articles/10.3389/fphys.2021.744730/fullhttps://www.frontiersin.org/articles/10.3389/fphys.2021.744730/supplementary-material/10.3389/fphys.2021.744730.s001},
	author = {Andrew G {Edwards} and M{\o}rk, Halvor and Mathis K. {Stokke} and David B. {Lipsett} and Sjaastad, Ivar and Richard, Sylvain and Ole M. {Sejersted} and William E. {Louch}}
}
@article {28306,
	title = {Sex-Specific Classification of Drug-Induced Torsade de Pointes Susceptibility Using Cardiac Simulations and Machine Learning},
	journal = {Clinical Pharmacology \& Therapeutics},
	volume = {1105970708108167},
	year = {2021},
	month = {Jan-08-2021},
	pages = {380 - 391},
	publisher = {Wiley},
	issn = {0009-9236},
	doi = {10.1002/cpt.v110.210.1002/cpt.2240},
	url = {https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1002/cpt.2240},
	author = {Alex Fogli {Iseppe} and Ni, Haibo and Zhu, Sicheng and Zhang, Xianwei and Coppini, Raffaele and Yang, Pei-Chi and Srivatsa, Uma and Colleen E. {Clancy} and Andrew G {Edwards} and Morotti, Stefano and Grandi, Eleonora}
}
@misc {shen20203d,
	title = {3D Dstorm Imaging Reveals Camkii-Dependent Dispersal of Ryanodine Receptor Clusters in Failing Rat Cardiomyocytes},
	howpublished = {Biophysical Journal},
	year = {2020},
	publisher = {Cell Press},
	address = {Biophysical Journal},
	author = {Shen, Xin and Terje R {Kolstad} and van den Brink, Jonas and Frisk, Michael and Hou, Yufeng and Norden, Einar and Andrew G {Edwards} and Sjaastad, Ivar and Soeller, Christian and William E {Louch}}
}
@article {27048,
	title = {A computational study on integrated mechanisms of mechano-electric feedback in ischemic arrhythmogenesis},
	journal = {SAGE},
	year = {2020},
	publisher = {Clinical Medicine Insights: Cardiology},
	author = {Timmermann, Viviane and Alexander T. {Quinn} and Sundnes, Joakim and Wall, Samuel and Andrew D. {McCulloch} and Andrew G {Edwards}}
}
@article {27665,
	title = {In Vitro Safety {\textquotedblleft}Clinical Trial{\textquotedblright} of the Cardiac Liability of Hydroxychloroquine and Azithromycin as COVID19 Polytherapy},
	journal = {Clinical Pharmacology \& Therapeutics},
	year = {2020},
	publisher = { Wiley},
	author = {Charrez, B{\'e}r{\'e}nice and Charwat, Verena and Siemons, Brian and Finsberg, Henrik and Miller, Evan and Andrew G {Edwards} and Kevin E. {Healy}}
}
@article {maki-marttunen2020unified,
	title = {A unified computational model for cortical post-synaptic plasticity},
	journal = {eLife},
	volume = {9},
	year = {2020},
	publisher = {Cold Spring Harbor Laboratory},
	author = {M{\"a}ki-Marttunen, Tuomo and Iannella, Nicolangelo and Andrew G {Edwards} and Gaute T. {Einevoll} and Kim T {Blackwell}}
}
@article {26347,
	title = {3D dSTORM imaging reveals novel detail of ryanodine receptor localization in rat cardiac myocytes},
	journal = {The Journal of Physiology},
	volume = {597},
	year = {2019},
	month = {Jan-15-2019},
	pages = {399-418},
	publisher = { Wiley-Blackwell},
	doi = {10.1113/jp277360},
	url = {https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP277360},
	author = {Shen, Xin and van den Brink, Jonas and Hou, Yufeng and Colli, Dylan and Le, Christopher and Terje R. {Kolstad} and MacQuaide, Niall and Cathrine R. {Carlson} and Peter M. {Kekenes-Huskey} and Andrew G {Edwards} and Soeller, Christian and William E. {Louch}}
}
@article {timmermann2019arrhythmogenic,
	title = {Arrhythmogenic current generation by myofilament-triggered Ca2+ release and sarcomere heterogeneity},
	journal = {Biophysical Journal},
	volume = {117},
	year = {2019},
	pages = {2471-2485},
	publisher = {Cell Press},
	author = {Timmermann, Viviane and Andrew G {Edwards} and Wall, Samuel and Sundnes, Joakim and Andrew D. {McCulloch}}
}
@article {maki2019biophysical,
	title = {Biophysical Psychiatry{\textemdash}How Computational Neuroscience Can Help to Understand the Complex Mechanisms of Mental Disorders},
	journal = {Frontiers in psychiatry},
	volume = {10},
	number = {534},
	year = {2019},
	publisher = {Frontiers Media SA},
	author = {M{\"a}ki-Marttunen, Tuomo and Kaufmann, Tobias and Elvs\aashagen, Torbj{\o}rn and Devor, Anna and Djurovic, Srdjan and Lars T {Westlye} and Linne, Marja-Leena and Rietschel, Marcella and Schubert, Dirk and Borgwardt, Stefan and Efrim-Budisteanu, M and Bettella, F and Halnes, G and Hagen, E and N{\ae}ss, Solveig and T V {Ness} and Moberget, T and Metzner, C and Andrew G {Edwards} and Fyhn, M and A M {Dale} and G T {Einevoll} and O A {Andreassen}}
}
@misc {27046,
	title = {A one-dimensional computational study of mechano-electric feedback and arrhythmogenic current generation},
	howpublished = {Gordon Research Conference "Cardiac Arrhythmia Mechanisms", Barga, Italy},
	year = {2019},
	author = {Timmermann, Viviane and Sundnes, Joakim and Wall, Samuel and Andrew D. {McCulloch} and Andrew G {Edwards}}
}
@article {26640,
	title = {Properties of cardiac conduction in a cell-based computational model},
	journal = {PLoS Computational Biology},
	volume = {15},
	number = {e1007042},
	year = {2019},
	month = {05/2019},
	publisher = {Public Library of Science},
	abstract = {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.},
	doi = {10.1371/journal.pcbi.1007042},
	url = {https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007042},
	author = {Karoline Horgmo {J{\ae}ger} and Andrew G {Edwards} and Andrew D. {McCulloch} and Tveito, Aslak}
}
@article {maki2018alterations,
	title = {Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations},
	journal = {Cerebral Cortex},
	volume = {29},
	number = {2},
	year = {2018},
	pages = {875{\textendash}891},
	publisher = {{Oxford University Press},
	author = {M{\"a}ki-Marttunen, Tuomo and Krull, Florian and Bettella, Francesco and Hagen, Espen and N{\ae}ss, Solveig and Torbj{\o}rn V {Ness} and Moberget, Torgeir and Elvs\aashagen, Torbj{\o}rn and Metzner, Christoph and Devor, Anna and Andrew G {Edwards} and Fyhn, M and Djurovic, S and A M {Dale} and O A {Andreassen} and G T {Einevoll}}
}
@article {26116,
	title = {Computational Modeling of Electrophysiology and Pharmacotherapy of Atrial Fibrillation: Recent Advances and Future Challenges},
	journal = {Frontiers in Physiology},
	volume = {9},
	year = {2018},
	month = {Apr-09-2018},
	pages = {1221},
	publisher = {Frontiers in Physiology},
	doi = {10.3389/fphys.2018.01221},
	url = {https://www.frontiersin.org/article/10.3389/fphys.2018.01221/fullhttps://www.frontiersin.org/article/10.3389/fphys.2018.01221/full},
	author = {Vagos, Marcia and Ilsbeth Gerarda Ma {van Herck} and Sundnes, Joakim and Arevalo, Hermenegild and Andrew G {Edwards} and Koivum{\"a}ki, Jussi}
}
@misc {27045,
	title = {A computational study of the contribution of mechano-electric feedback to arrhythmogenic current generation},
	howpublished = {Berlin, Germany},
	year = {2018},
	publisher = {Heart by Numbers, Biophysical Society},
	author = {Timmermann, Viviane and Sundnes, Joakim and Wall, Samuel and Andrew D. {McCulloch} and Andrew G {Edwards}}
}
@misc {43143,
	title = {In silico Model of Gating Kinetics, Temperature Dependence and Calcium Sensitivity of the SK Channel},
	year = {2018},
	month = {09/2018},
	type = {Conference Poster},
	address = {Biophysical Society Thematic Meeting: The Heart by Numbers},
	abstract = {The small conductance calcium activated potassium (SK) channel affects atrial repolarization and is implicated in the onset and progression of atrial fibrillation (AF). In vitro, in vivo and genetic studies have provided functional and molecular links between SK channels and AF. SK inhibition promotes AF termination and protects against AF re-induction in large animal models, but the effect of SK modulation in humans remains limited and controversial.Objective: To provide a detailed computational SK model for interrogating the role of these channels in human atrial electrophysiology and arrhythmogenesis.Methods and Results: We have constructed a detailed Markov SK model from single channel and excised inside-out macropatch recordings. Single channel data confirmed the previously reported gating structure of neuronal SK2 channels (4 closed and 2 open states), and were used to define the transition kinetics for calcium-dependent SK activation. Inside-out macropatch recordings uncovered a strong temperature-dependence of SK Ca2+-sensitivity. At room temperature, the EC50 for hSK2 and hSK3 was 0.38 {\textpm} 0.02 {\textmu}M and 0.53 {\textpm} 0.07 {\textmu}M, respectively. Increasing the temperature to 37{\textdegree}C shifted SK Ca2+-sensitivity towards the diastolic range for both hSK2 and hSK3 (EC50 = 0.22 {\textpm} 0.01 {\textmu}M and 0.18 {\textpm} 0.02 {\textmu}M, respectively). The associated Q10 values were 1.44 (hSK2) and 2.05 (hSK3). \&nbsp;This temperature dependence will be incorporated into the Markovian formulation, which itself will be embedded in a human atrial myocyte model and tissue constructs, to assess the implications for SK channel function in vivo.Conclusions: The novel temperature dependence of SK channel Ca2+-sensitivity indicates partial channel activity during atrial diastole. This finding implies that SK channel localization may be less important than previously assumed, and that SK channels may be capable of modulating atrial resting potential and repolarization, particularly during calcium overload and AF.},
	author = {Ilsbeth Gerarda Ma {van Herck} and Bo H {Bentzen} and Seutin, Vincent and Koivum{\"a}ki, Jussi and Maleckar, Molly and Neil V {Marrion} and Andrew G {Edwards}}
}
@misc {26383,
	title = {In Silico Modeling of Cardiac Microphysiological  Systems for Evaluating Drug Side Effects},
	howpublished = {Heart By Numbers Conference, Berlin, Germany},
	year = {2018},
	author = {Wall, Samuel and Tveito, Aslak and Karoline Horgmo {J{\ae}ger} and Andrew G {Edwards} and Healy, Kevin and Huebsch, Nathaniel and Charrez, B{\'e}r{\'e}nice}
}
@article {26238,
	title = {Inversion and computational maturation of drug response using human stem cell derived cardiomyocytes in microphysiological systems},
	journal = {Nature Scientific Reports },
	volume = {8},
	number = {17626},
	year = {2018},
	month = {12/2018},
	publisher = {Springer Nature},
	abstract = {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.},
	doi = {10.1038/s41598-018-35858-7},
	url = {https://doi.org/10.1038/s41598-018-35858-7},
	author = {Tveito, Aslak and Karoline Horgmo {J{\ae}ger} and Huebsch, Nathaniel and Charrez, B{\'e}r{\'e}nice and Andrew G {Edwards} and Wall, Samuel and Kevin E. {Healy}}
}
@article {Huebsch485169,
	title = {Metabolically-Driven Maturation of hiPSC-Cell Derived Heart-on-a-Chip},
	journal = {{bioRxiv},
	year = {2018},
	publisher = {Cold Spring Harbor Laboratory},
	abstract = {Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) are a promising in vitro tool for drug development and disease modeling, but their immature electrophysiology limits their diagnostic utility. Tissue engineering approaches involving aligned and 3D culture enhance hiPSC-CM maturation but are insufficient to induce electrophysiological maturation. We hypothesized that recapitulating post-natal switching of the heart{\textquoteright}s primary adenosine triphosphate source from glycolysis to fatty acid oxidation could enhance maturation of hiPSC-CM. We combined hiPSC-CM with microfabrication to create 3D cardiac microphysiological systems (MPS) that enhanced immediate microtissue alignment and tissue specific extracellular matrix production. Using Robust Experimental design, we identified a maturation media that allowed the cardiac MPS to correctly assess false positive and negative drug response. Finally, we employed mathematical modeling and gene expression data to explain the observed changes in electrophysiology and pharmacology of MPS exposed to maturation media. In contrast, the same media had no effects on 2D hiPSC-CM monolayers. These results suggest that systematic combination of biophysical stimuli and metabolic cues can enhance the electrophysiological maturation of hiPSC-derived cardiomyocytes.},
	doi = {10.1101/485169},
	url = {https://www.biorxiv.org/content/early/2018/12/10/485169},
	author = {Huebsch, Nathaniel and Charrez, Berenice and Siemons, Brian and Steven C. {Boggess} and Wall, Samuel and Charwat, Verena and Jaeger, Karoline and Felipe Lee T. {Montiel} and Nicholas C. {Jeffreys} and Deveshwar, Nikhil and Andrew G {Edwards} and Serrano, Jonathan and Snuderl, Matija and Stahl, Andreas and Tveito, Aslak and Evan W. {Miller} and Kevin E. {Healy}}
}
@misc {43144,
	title = {Model development of SK channel gating incorporating calcium sensitivity and drug interaction},
	year = {2018},
	month = {02/2018},
	type = {Conference Poster},
	address = {Biophysical Society 62nd Annual Meeting, San Francisco CA},
	abstract = {Small conductance calcium activated potassium (SK) channels are predominantly expressed in heart atria and contribute to late repolarization of the action potential. Inhibition of SK current has been proposed as a therapy for atrial fibrillation (AF). We aim to develop an accurate model of SK channel gating and drug interaction that can be used to probe the role of SK channel in atrial health and disease.\&nbsp;The model, based on Hirschberg et al{\textquoteright}s (1998) SK2 model, incorporates 4 closed and 2 open states. To generate a model with utility at physiologic temperature, we performed inside-out macropatch voltage clamp ramps at 23{\textdegree} and 37{\textdegree}C, and observed a pronounced leftward EC50 shift at 37{\textdegree}C (0.53 {\textpm} 0.07\&nbsp;{\textmu}M and 0.38 {\textpm} 0.02\&nbsp;{\textmu}M to\&nbsp;0.23 {\textpm} 0.02\&nbsp;{\textmu}M and 0.28 {\textpm} 0.01\&nbsp;{\textmu}M for hSK3 and hSK2, respectively). Thus, taking calcium activation of the major hSK isoforms into the diastolic calcium range. To provide a first-principles basis for constraining the kinetics of multi-step calcium-dependent activation, and binding of known and novel pharmacologic inhibitors, we performed single0channel recordings of SK2 at 23{\textdegree}C. Opening events without inhibitors were best fit with two major open-state conductances (low: 10.9 {\textpm} 1.6 pS, 60 {\textpm} 41\% of events; high: 14.9 {\textpm} 1.4 pS, 40 {\textpm} 41\% of events), justifying the multiple open states included in the model and to be further analysed regarding state specific kinetics. We will also present single channel data on known inhibitor apamin and novel modulator AP14145 constraining a pharmacological model. In conclusion, these experiments provided novel findings on temperature sensitivity of SK channel. These will be incorporated into an improved Markov model of SK channel dynamics to elucidate the roles of SK channels in health and disease.\&nbsp;},
	author = {Ilsbeth Gerarda Ma {van Herck} and Bo H {Bentzen} and Seutin, Vincent and Arevalo, Hermenegild and Maleckar, Molly and Neil V {Marrion} and Andrew G {Edwards}}
}
@article {van2018model,
	title = {Model development of sk channel gating incorporating calcium sensitivity and drug interaction},
	journal = {Biophysical Journal},
	volume = {114},
	number = {3},
	year = {2018},
	pages = {306a},
	publisher = {{Elsevier},
	author = {van Herck, Ilse and Bo H {Bentzen} and Seutin, Vincent and Arevalo, Hermenegild and Maleckar, Molly and Neil V {Marrion} and Andrew G {Edwards}}
}
@article {26326,
	title = {Ryanodine Receptor Dispersion Disrupts Ca2+-Release in Failing Cardiac Myocytes},
	journal = {eLife},
	volume = {7},
	year = {2018},
	month = {10/2018},
	pages = {e39427},
	publisher = {eLife Sciences Publications},
	issn = {2050-084X},
	doi = {10.7554/eLife.39427},
	url = {https://elifesciences.org/articles/39427},
	author = {Terje R {Kolstad} and van den Brink, Jonas and MacQuaide, Niall and Per Kristian {Lunde} and Frisk, Michael and Jan Magnus {Aronsen} and Einar S {Norden} and Cataliotti, Alessandro and Sjaastad, Ivar and Ole M {Sejersted} and Andrew G {Edwards} and Glenn T. {Lines} and William E {Louch}}
}
@article {24994,
	title = {An Evaluation of the Accuracy of Classical Models for Computing the Membrane Potential and Extracellular Potential for Neurons},
	journal = {Frontiers in Computational Neuroscience},
	volume = {11},
	year = {2017},
	pages = {27},
	publisher = {Frontiers Media SA},
	abstract = {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\&nbsp;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 \&ndash; 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.},
	issn = {1662-5188},
	doi = {10.3389/fncom.2017.00027},
	url = {http://journal.frontiersin.org/article/10.3389/fncom.2017.00027},
	author = {Tveito, Aslak and Karoline Horgmo {J{\ae}ger} and Glenn T. {Lines} and Paszkowski, {\L}ukasz and Sundnes, Joakim and Andrew G {Edwards} and M{\"a}ki-Marttunen, Tuomo and Halnes, Geir and Gaute T {Einevoll}}
}
@misc {25790,
	title = {Integrated Mechanisms of Mechano-Electric feedback in Ischemic Arrhythmogenesis},
	howpublished = {Bergen, Norway},
	year = {2017},
	author = {Timmermann, Viviane and Andrew G {Edwards} and Sundnes, Joakim and Andrew D. {McCulloch} and Wall, Samuel and T. A. {Quinn}}
}
@misc {25792,
	title = {Integrated Mechanisms of Mechano-Electric Feedback in Ischemic Arrhythmogenesis},
	year = {2017},
	month = {09/2017},
	address = {Oslo, Norway},
	author = {Timmermann, Viviane and Wall, Samuel and Sundnes, Joakim and T. A. {Quinn} and Andrew G {Edwards}}
}
@article {25788,
	title = {An integrative appraisal of mechano-electric feedback mechanisms in the heart},
	journal = {Progress in biophysics and molecular biology},
	volume = {130},
	year = {2017},
	pages = {404{\textendash}417},
	publisher = {Elsevier},
	author = {Timmermann, Viviane and Lars A {Dejgaard} and Kristina H {Haugaa} and Andrew G {Edwards} and Sundnes, Joakim and Andrew D. {McCulloch} and Wall, Samuel}
}
@article {25774,
	title = {Pleiotropic effects of schizophrenia-associated genetic variants in neuron firing and cardiac pacemaking revealed by computational modeling},
	journal = {Translational Psychiatry},
	volume = {7},
	number = {11},
	year = {2017},
	pages = {5},
	publisher = {Nature Publishing Group},
	author = {M{\"a}ki-Marttunen, Tuomo and Glenn T. {Lines} and Andrew G {Edwards} and Tveito, Aslak and Anders M {Dale} and Gaute T {Einevoll} and Ole A {Andreassen}}
}
@misc {25789,
	title = {Role of Electromechanical Feedback in Stretch Induced Arrhythmias : From Single Myocyte to Multicellular Level},
	year = {2017},
	month = {02/2017},
	address = {Gordon Research Conference on Arrhythmia Mechanisms, Ventura, California, USA},
	author = {Timmermann, Viviane and Lars A {Dejgaard} and Andrew D. {McCulloch} and Kristina H {Haugaa} and Andrew G {Edwards} and Wall, Samuel}
}
@misc {43145,
	title = {Small conductance calcium activated potassium channel: pharmacology and binding scheme for in silico model},
	year = {2017},
	month = {06/2017},
	type = {Poster},
	address = {Copenhagen Meeting on Cardiac Arrhythmia},
	author = {Ilsbeth Gerarda Ma {van Herck} and Rafel Sim{\'o} {Vicens} and Arevalo, Hermenegild and Koivum{\"a}ki, Jussi and Bo H {Bentzen} and Andrew G {Edwards}}
}
@article {25832,
	title = {Species-Dependent Mechanisms of Cardiac Arrhythmia: A Cellular Focus},
	journal = {Clinical Medicine Insights: Cardiology},
	volume = {11},
	year = {2017},
	publisher = { SAGE Publications},
	issn = {1179-5468},
	doi = {10.1177/1179546816686061},
	author = {Andrew G {Edwards} and William Edward {Louch}}
}
@article {24963,
	title = {Studying dyadic structure-function relationships: a review of current modeling approaches and new insights into Ca2+ (mis)handling},
	journal = {Clinical Medicine Insights: Cardiology},
	volume = {11},
	year = {2017},
	month = {04/2017},
	pages = {1-11},
	publisher = {Libertas Academica},
	doi = { 10.1177/1179546817698602},
	url = {http://insights.sagepub.com/studying-dyadic-structurefunction-relationships-a-review-of-current-mo-article-a6287},
	author = {Maleckar, Molly and Andrew G {Edwards} and Louch, William and Glenn T. {Lines}}
}
@article {maleckar2017studying,
	title = {Studying dyadic structure{\textendash}function relationships: a review of current modeling approaches and new insights into ca2+ (mis) handling},
	journal = {Clinical Medicine Insights: Cardiology},
	volume = {11},
	year = {2017},
	pages = {1179546817698602},
	publisher = {{SAGE Publications Sage UK: London, England},
	author = {Maleckar, Molly and Andrew G {Edwards} and William E {Louch} and Glenn T. {Lines}}
}
@article {23677,
	title = {Atrial-selective targeting of arrhythmogenic phase-3 early afterdepolarizations in human myocytes},
	journal = {Journal of Molecular and Cellular Cardiology},
	volume = {96},
	year = {2016},
	pages = {63-71},
	publisher = {Academic Press},
	author = {Morotti, Stefano and Andrew D. {McCulloch} and Donald M. {Bers} and Andrew G {Edwards} and Grandi, Eleonora}
}
@inbook {Simula.simula.2290,
	title = {Calcium Signaling in Cardiomyocyte Models With Realistic Geometries (7th Edition)},
	booktitle = {Cardiac Electrophysiology: From Cell to Bedside},
	year = {2016},
	publisher = {Elsevier Science},
	organization = {Elsevier Science},
	edition = {7},
	chapter = {33},
	isbn = {9781455728565},
	author = {Andrew G {Edwards} and Johan Elon {Hake} and Anushka P. {Michailova} and Hoshijima, Masahiko and Andrew D. {McCulloch}},
	editor = {Zipes, Douglas and Jalife, Jose}
}
@article {24996,
	title = {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},
	journal = {Mathematical Biosciences},
	volume = {277},
	year = {2016},
	pages = {126-135},
	publisher = {Elsevier Inc},
	author = {Tveito, Aslak and Glenn T. {Lines} and Andrew G {Edwards} and Andrew D. {McCulloch}}
}
@misc {25791,
	title = {Role of Electromechanical Feedback in Mitral Valve Prolapse Arrhythmia},
	year = {2016},
	month = {09/2016},
	publisher = {Conference on Cardiac Mechano-Electric Couping and Arrhythmias},
	address = {Freiburg, Germany},
	author = {Timmermann, Viviane and Andrew G {Edwards} and Sundnes, Joakim and Andrew D. {McCulloch} and Wall, Samuel}
}
@article {23810,
	title = {Atrial-selective targeting of arrhythmogenic phase-3 early afterdepolarizations in human myocytes},
	journal = {Journal of Molecular and Cellular Cardiology},
	volume = {In Press},
	year = {2015},
	publisher = {Academic Press},
	author = {Morotti, Stefano and Andrew D. {McCulloch} and Donald M. {Bers} and Andrew G {Edwards} and Grandi, Eleonora}
}
@article {23678,
	title = {Na+/Ca2+ exchange and Na+/K+-ATPase in the heart},
	journal = {The Journal of Physiology},
	volume = {593},
	year = {2015},
	pages = {1361-1382},
	publisher = {John Wiley \& Sons},
	author = {Michael J {Shattock} and Ottolia, Michela and Donald M. {Bers} and Mordecai P {Blaustein} and Andr {Boguslavskyi, ii} and Bossuyt, Julie and John HB {Bridge} and Chen-Izu, Ye and Colleen E {Clancy} and Andrew G {Edwards}}
}
@misc {morotti2015ranolazine,
	title = {Ranolazine Prevents Phase-3 Early Afterdepolarizations in Human Atrial Myocytes by Inhibiting Na Current Non-Equilibrium Reactivation},
	howpublished = {Biophysical Society annual meeting},
	year = {2015},
	month = {01/27/2015},
	pages = {195a{\textendash}196a},
	publisher = {Elsevier},
	author = {Morotti, Stefano and Andrew D. {McCulloch} and Donald M. {Bers} and Andrew G {Edwards} and Grandi, Eleonora}
}
@misc {23679,
	title = {Secretoneurin, a Novel Endogenous CaMKII Inhibitor, Augments Cardiomyocyte Calcium Handling and Inhibits Arrhythmogenic Calcium Release},
	howpublished = {Biophysical Journal},
	volume = {108},
	number = {2},
	year = {2015},
	pages = {340a},
	publisher = {Elsevier},
	author = {Anett H {Ottesen} and Cathrine R {Carlson} and Andrew G {Edwards} and Ole JB {Landsverk} and Johansen, Rune and Morten K {Moe} and Bj{\o}raas, Magnar and Stridsberg, Mats and Omland, Torbj{\o}rn and Christensen, Geir and R{\o}sj{\o}, Helge}
}
@article {23348,
	title = {CaMKII comes of age in cardiac health and disease.},
	journal = {Frontiers in pharmacology},
	year = {2014},
	publisher = {Frontiers Media S.A.},
	author = {Grandi, Eleonora and Andrew G {Edwards} and Anthony W {Herren} and Donald M. {Bers}}
}
@article {23682,
	title = {CaMKII comes of age in cardiac health and disease},
	journal = {Frontiers in Pharmacology},
	volume = {5},
	year = {2014},
	publisher = {Frontiers Media SA},
	author = {Grandi, Eleonora and Andrew G {Edwards} and Anthony W {Herren} and Donald M. {Bers}}
}
@article {23680,
	title = {Caveolae in ventricular myocytes are required for stretch-dependent conduction slowing},
	journal = {Journal of Molecular and Cellular Cardiology},
	volume = {76},
	year = {2014},
	pages = {265-274},
	publisher = {Academic Press},
	author = {Pfeiffer, ER and Wright, AT and Andrew G {Edwards} and Stowe, JC and McNall, K and Tan, J and Niesman, I and Patel, HH and Roth, DM and Omens, JH and Andrew D. {McCulloch}}
}
@inproceedings {23356,
	title = {A Markov-State Model for the Regulation of the Sarcoplasmic Reticulum Ca2+ ATPase by Phospholamban},
	journal = {Annual meeting in Biophysical society},
	volume = {106},
	year = {2014},
	month = {01/2014},
	publisher = {Elsevier},
	abstract = {Compelling evidence suggests that reduced sarcoplasmic reticulum (SR) Ca 2+ uptake via\&nbsp;the SR Ca 2+ ATPase (SERCA) is a major contributor to the development of Ca 2+ signaling\&nbsp;abnormalities in heart failure, and equally important as other known contributors to impaired\&nbsp;Ca 2+ handling.},
	author = {Peter M. {Kekenes-Huskey} and Andrew G {Edwards} and Johan Elon {Hake} and Anushka P. {Michailova} and Andrew J. {McCammon} and Andrew D. {McCulloch}}
}
@article {23336,
	title = {Non-equilibrium reactivation of Na+ current drives early afterdepolarizations in mouse ventricle},
	journal = {Circulation: Arrhythmia and Electrophysiology},
	volume = {7},
	year = {2014},
	pages = {1205-1213},
	publisher = {Lippincott Williams \& Wilkins (United States)},
	address = {Worldwide},
	author = {Andrew G {Edwards} and Grandi, Eleonora and Johan Elon {Hake} and Patel, Sonia and Li, Pan and Miyamoto, Shigeki and Jeffrey H. {Omens} and Joan Heller {Brown} and Donald M. {Bers} and Andrew D. {McCulloch}}
}
@article {23347,
	title = {A novel computational model of mouse myocyte electrophysiology to assess the synergy between Na+ loading and CaMKII},
	journal = {The Journal of physiology},
	volume = {592},
	year = {2014},
	month = {03/2014},
	pages = {1181-1197},
	publisher = {Wiley-Blackwell},
	author = {Morotti, S and Andrew G {Edwards} and Andrew D. {McCulloch} and Donald M. {Bers} and Grandi, Eleonora}
}
@article {23683,
	title = {A novel computational model of mouse myocyte electrophysiology to assess the synergy between Na+ loading and CaMKII},
	journal = {The Journal of Physiology},
	volume = {592},
	year = {2014},
	pages = {1181-1197},
	publisher = {John Wiley \& Sons},
	author = {Morotti, S and Andrew G {Edwards} and Andrew D. {McCulloch} and Donald M. {Bers} and Grandi, Eleonora}
}
@article {23681,
	title = {Toward a hierarchy of mechanisms in CaMKII-mediated arrhythmia},
	journal = {Frontiers in Pharmacology},
	volume = {5},
	year = {2014},
	publisher = {Frontiers Media SA},
	author = {Kevin P {Vincent} and Andrew D. {McCulloch} and Andrew G {Edwards}}
}
@article {23340,
	title = {Toward a hierarchy of mechanisms in CaMKII-mediated arrhythmia},
	journal = {Frontiers in Pharmacology},
	volume = {5},
	year = {2014},
	publisher = {Frontiers Media S.A.},
	author = {Kevin P {Vincent} and Andrew D. {McCulloch} and Andrew G {Edwards}}
}
@inbook {Simula.simula.2290,
	title = {Calcium Signaling in Cardiomyocyte Models With Realistic Geometries (6th Edition)},
	booktitle = {Cardiac Electrophysiology: From Cell to Bedside },
	year = {2013},
	month = {2013},
	pages = {33.1-33.10},
	publisher = {Elsevier Science},
	organization = {Elsevier Science},
	edition = {6},
	chapter = {33},
	isbn = {9781455728565},
	author = {Anushka P. {Michailova} and Andrew G {Edwards} and Johan Elon {Hake} and Hoshijima, Masahiko and Andrew D. {McCulloch}},
	editor = {Zipes, Douglas and Jalife, Jose}
}
@article {23809,
	title = {Conference report from the 2012 AHA scientific sessions in Los Angeles},
	journal = {Expert Opinion on Therapeutic Targets},
	volume = {17},
	year = {2013},
	pages = {733-737},
	publisher = {Informa UK, Ltd. London},
	author = {Westenbrink, Daan and Andrew G {Edwards} and Miyamoto, Shigeki}
}
@article {23684,
	title = {The promise of CaMKII inhibition for heart disease: preventing heart failure and arrhythmias},
	journal = {Expert opinion on therapeutic targets},
	volume = {17},
	year = {2013},
	pages = {889-993},
	publisher = {Informa UK, Ltd. London},
	author = {Westenbrink, Daan and Andrew G {Edwards} and Andrew D. {McCulloch} and Joan Heller {Brown}}
}
@article {Simula.simula.720,
	title = {Instabilities of the Resting State in a Mathematical Model of Calcium Handling in Cardiac Myocytes},
	journal = {Mathematical Biosciences},
	volume = {236},
	number = {2},
	year = {2012},
	pages = {97-107},
	publisher = {Elsevier},
	doi = {http://dx.doi.org/10.1016/j.mbs.2012.02.005},
	author = {Tveito, Aslak and Glenn T. {Lines} and Johan Elon {Hake} and Andrew G {Edwards}}
}
@misc {Simula.simula.1410,
	title = {Modeling Calcium Sparks in a Three-Dimensional Reconstruction of a Cardiac Calcium Release Unit},
	year = {2012},
	author = {Johan Elon {Hake} and Andrew G {Edwards} and Yu, Z. and Peter M. {Kekenes-Huskey} and Anushka P. {Michailova} and Andrew J. {McCammon} and Michael J. {Holst} and Hoshijima, Masahiko and Andrew D. {McCulloch}}
}
@article {Simula.simula.1318,
	title = {Modeling Cardiac Calcium Sparks in a Three-Dimensional Reconstruction of a Calcium Release Unit},
	journal = {The Journal of Physiology},
	volume = {590},
	number = {18},
	year = {2012},
	month = {Sept},
	pages = {4403-4422},
	author = {Johan Elon {Hake} and Andrew G {Edwards} and Yu, Z. and Peter M. {Kekenes-Huskey} and Anushka P. {Michailova} and Andrew J. {McCammon} and Michael J. {Holst} and Hoshijima, Masahiko and Andrew D. {McCulloch}}
}
@article {Slow-Calcium-Depolarization-Calcium,
	title = {Slow Calcium-Depolarization-Calcium Waves May Initiate Fast Local Depolarization Waves in Ventricular Tissue},
	journal = {Progress in Biophysics and Molecular Biology},
	volume = {110},
	number = {2-3},
	year = {2012},
	month = {July 24},
	pages = {295-304},
	abstract = {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.},
	author = {Tveito, Aslak and Glenn T. {Lines} and Andrew G {Edwards} and Maleckar, Molly and Anushka P. {Michailova} and Johan Elon {Hake} and Andrew D. {McCulloch}}
}
@misc {Simula.simula.1414,
	title = {βAR-Stimulation Causes EADs But Not DADs in Pre-Failure CAMKIIδC Transgenic Myocytes},
	howpublished = {Biophysical Society annual meeting},
	year = {2012},
	author = {Andrew G {Edwards} and Johan Elon {Hake} and Joan Heller {Brown} and Andrew D. {McCulloch}}
}
@article {23687,
	title = {Measuring changes in aerodynamic/rolling resistances by cycle-mounted power meters},
	journal = {Medicine and science in sports and exercise},
	volume = {43},
	year = {2011},
	pages = {853-860},
	publisher = {Wolters Kluwer},
	author = {Allen C {Lim} and Eric P {Homestead} and Andrew G {Edwards} and Todd C {Carver} and Kram, Rodger and William C {Byrnes}}
}
@article {23808,
	title = {What for nature, and who to nurture?},
	journal = {Journal of Applied Physiology},
	volume = {110},
	year = {2011},
	publisher = {American Physiological Society},
	author = {Anthony J {Donato} and Andrew G {Edwards}}
}
@article {23688,
	title = {What for nature, and who to nurture?},
	journal = {Journal of Applied Physiology},
	volume = {110},
	year = {2011},
	publisher = {American Physiological Society},
	author = {Anthony J {Donato} and Andrew G {Edwards}}
}
@article {23685,
	title = {Accuracy of optimized branched algorithms to assess activity-specific PAEE},
	journal = {Medicine and science in sports and exercise},
	volume = {42},
	year = {2010},
	pages = {672},
	publisher = {NIH Public Access},
	author = {Andrew G {Edwards} and James O {Hill} and William C {Byrnes} and Raymond C {Browning}}
}
@article {23690,
	title = {Life-long caloric restriction elicits pronounced protection of the aged myocardium: a role for AMPK},
	journal = {Mechanisms of ageing and development},
	volume = {131},
	year = {2010},
	pages = {739-742},
	publisher = {Elsevier},
	author = {Andrew G {Edwards} and Anthony J {Donato} and Lisa A {Lesniewski} and Rachel A {Gioscia} and Douglas R {Seals} and Russell L {Moore}}
}
@article {23811,
	title = {Life-long caloric restriction elicits pronounced protection of the aged myocardium: a role for AMPK},
	journal = {Mechanisms of Aging and Development},
	volume = {131},
	year = {2010},
	pages = {739-742},
	publisher = {Elsevier},
	author = {Andrew G {Edwards} and Anthony J {Donato} and Lisa A {Lesniewski} and Rachel A {Gioscia} and Douglas R {Seals} and Russell L {Moore}}
}
@article {23689,
	title = {PKC-permitted elevation of sarcolemmal KATP concentration may explain female-specific resistance to myocardial infarction},
	journal = {The Journal of Physiology},
	volume = {587},
	year = {2009},
	pages = {5723-5737},
	publisher = {Blackwell Publishing Ltd},
	author = {Andrew G {Edwards} and Meredith L {Rees} and Rachel A {Gioscia} and Derek K {Zachman} and Joshua M {Lynch} and Jason C {Browder} and Adam J {Chicco} and Russell L {Moore}}
}
@article {23686,
	title = {Aerodynamic characteristics as determinants of the drafting effect in cycling.},
	journal = {Medicine and science in sports and exercise},
	volume = {39},
	year = {2007},
	pages = {170-176},
	publisher = {Wolters Kluwer},
	author = {Andrew G {Edwards} and William C {Byrnes}}
}
