All Outputs (99)

Connexin43 contributes to electrotonic conduction across scar tissue in the intact heart (2016)
Journal Article
Mahoney, V., Mezzano, V., Mirams, G., Maass, K., Li, Z., Cerrone, M., …Morley, G. (2016). Connexin43 contributes to electrotonic conduction across scar tissue in the intact heart. Scientific Reports, 6(1), Article 26744. https://doi.org/10.1038/srep26744

Studies have demonstrated non-myocytes, including fibroblasts, can electrically couple to myocytes in culture. However, evidence demonstrating current can passively spread across scar tissue in the intact heart remains elusive. We hypothesize electro... Read More about Connexin43 contributes to electrotonic conduction across scar tissue in the intact heart.

Hierarchical Bayesian modelling of variability and uncertainty in synthetic action potential traces (2016)
Journal Article
Johnstone, R. H., Bardenet, R., Gavaghan, D. J., Polonchuk, L., Davies, M. R., & Mirams, G. R. (2016). Hierarchical Bayesian modelling of variability and uncertainty in synthetic action potential traces. Computing in cardiology, 43, 1089-1092

© 2016 CCAL. There are many sources of uncertainty in the recording and modelling of membrane action potentials (APs) from cardiomyocytes. For example, there are measurement, parameter, and model uncertainties. There is also extrinsic variability bet... Read More about Hierarchical Bayesian modelling of variability and uncertainty in synthetic action potential traces.

Recent developments in using mechanistic cardiac modelling for drug safety evaluation (2016)
Journal Article
Davies, M. R., Wang, K., Mirams, G. R., Caruso, A., Noble, D., Walz, A., …Polonchuk, L. (2016). Recent developments in using mechanistic cardiac modelling for drug safety evaluation. Drug Discovery Today, 21(6), 924-938. https://doi.org/10.1016/j.drudis.2016.02.003

The Cardiac Electrophysiology Web Lab (2016)
Journal Article
Mirams, G., Cooper, J., & Scharm, M. (2016). The Cardiac Electrophysiology Web Lab. Biophysical Journal, 110(2), 292-300. https://doi.org/10.1016/j.bpj.2015.12.012

Uncertainty and variability in models of the cardiac action potential: Can we build trustworthy models? (2015)
Journal Article
Johnstone, R. H., Chang, E. T., Bardenet, R., de Boer, T. P., Gavaghan, D. J., Pathmanathan, P., …Mirams, G. R. (2016). Uncertainty and variability in models of the cardiac action potential: Can we build trustworthy models?. Journal of Molecular and Cellular Cardiology, 96, 49-62. https://doi.org/10.1016/j.yjmcc.2015.11.018

Cardiac electrophysiology models have been developed for over 50 years, and now include detailed descriptions of individual ion currents and sub-cellular calcium handling. It is commonly accepted that there are many uncertainties in these systems, wi... Read More about Uncertainty and variability in models of the cardiac action potential: Can we build trustworthy models?.

Mathematical Modelling of Heart Rate Changes in the Mouse (2015)
Report
Christie, M., Nandi, M., Borg, Y., Carapella, V., Mirams, G., Aston, P., …Chakrabarti, B. Mathematical Modelling of Heart Rate Changes in the Mouse. NC3Rs

The CVS is composed of numerous interacting and dynamically regulated physiological subsystems which each generate measurable periodic components such that the CVS can itself be presented as a system of weakly coupled oscillators. The interactions be... Read More about Mathematical Modelling of Heart Rate Changes in the Mouse.

Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential (2015)
Journal Article
Capel, R. A., Herring, N., Kalla, M., Yavari, A., Mirams, G. R., Douglas, G., …Burton, R. A. B. (2015). Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential. Heart Rhythm, 12(10), 2186-2194. https://doi.org/10.1016/j.hrthm.2015.05.027

© 2015 Heart Rhythm Society. Background Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate is an important determinant of myocardial oxygen consumption. Objectives The purpose of this study... Read More about Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential.

Ca2+ Channel Re-localization to Plasma-Membrane Microdomains Strengthens Activation of Ca2+-Dependent Nuclear Gene Expression (2015)
Journal Article
Samanta, K., Kar, P., Mirams, G. R., & Parekh, A. B. (2015). Ca2+ Channel Re-localization to Plasma-Membrane Microdomains Strengthens Activation of Ca2+-Dependent Nuclear Gene Expression. Cell Reports, 12(2), 203-216. https://doi.org/10.1016/j.celrep.2015.06.018

© 2015 The Authors. In polarized cells or cells with complex geometry, clustering of plasma-membrane (PM) ion channels is an effective mechanism for eliciting spatially restricted signals. However, channel clustering is also seen in cells with relati... Read More about Ca2+ Channel Re-localization to Plasma-Membrane Microdomains Strengthens Activation of Ca2+-Dependent Nuclear Gene Expression.

A web portal for in-silico action potential predictions (2015)
Journal Article
Williams, G., & Mirams, G. R. (2015). A web portal for in-silico action potential predictions. Journal of Pharmacological and Toxicological Methods, 75, 10-16. https://doi.org/10.1016/j.vascn.2015.05.002

© 2015 . Introduction: Multiple cardiac ion channels are prone to block by pharmaceutical compounds, and this can have large implications for cardiac safety. The effect of a compound on individual ion currents can now be measured in automated patch c... Read More about A web portal for in-silico action potential predictions.

Cardiac tissue slices: Preparation, handling, and successful optical mapping (2015)
Journal Article
Wang, K., Lee, P., Mirams, G. R., Sarathchandra, P., Borg, T. K., Gavaghan, D. J., …Bollensdorff, C. (2015). Cardiac tissue slices: Preparation, handling, and successful optical mapping. AJP - Heart and Circulatory Physiology, 308(9), H1112-H1125. https://doi.org/10.1152/ajpheart.00556.2014

© 2015 the American Physiological Society. Cardiac tissue slices are becoming increasingly popular as a model system for cardiac electrophysiology and pharmacology research and development. Here, we describe in detail the preparation, handling, and o... Read More about Cardiac tissue slices: Preparation, handling, and successful optical mapping.

Cellular cardiac electrophysiology modeling with Chaste and CellML (2015)
Journal Article
Cooper, J., Spiteri, R. J., & Mirams, G. R. (2015). Cellular cardiac electrophysiology modeling with Chaste and CellML. Frontiers in Physiology, 5, https://doi.org/10.3389/fphys.2014.00511

© 2015 Cooper, Spiteri and Mirams. Chaste is an open-source C++ library for computational biology that has well-developed cardiac electrophysiology tissue simulation support. In this paper, we introduce the features available for performing cardiac e... Read More about Cellular cardiac electrophysiology modeling with Chaste and CellML.

Application of stochastic phenomenological modelling to cell-to-cell and beat-to-beat electrophysiological variability in cardiac tissue (2014)
Journal Article
Walmsley, J., Mirams, G. R., Pitt-Francis, J., Rodriguez, B., & Burrage, K. (2015). Application of stochastic phenomenological modelling to cell-to-cell and beat-to-beat electrophysiological variability in cardiac tissue. Journal of Theoretical Biology, 365, 325-336. https://doi.org/10.1016/j.jtbi.2014.10.029

Prediction of Thorough QT study results using action potential simulations based on ion channel screens (2014)
Journal Article
Mirams, G. R., Davies, M. R., Brough, S. J., Bridgland-Taylor, M. H., Cui, Y., Gavaghan, D. J., & Abi-Gerges, N. (2014). Prediction of Thorough QT study results using action potential simulations based on ion channel screens. Journal of Pharmacological and Toxicological Methods, 70(3), 246-254. https://doi.org/10.1016/j.vascn.2014.07.002

Ten Simple Rules for Effective Computational Research (2014)
Journal Article
Osborne, J. M., Bernabeu, M. O., Bruna, M., Calderhead, B., Cooper, J., Dalchau, N., …Deane, C. (2014). Ten Simple Rules for Effective Computational Research. PLoS Computational Biology, 10(3), Article e1003506. https://doi.org/10.1371/journal.pcbi.1003506

Estimation of Conductivity Tensors from Human Ventricular Optical Mapping Recordings (2013)
Book Chapter
Walmsley, J., Mirams, G. R., Efimov, I. R., Burrage, K., & Rodriguez, B. (2013). Estimation of Conductivity Tensors from Human Ventricular Optical Mapping Recordings. In S. Ourselin, D. Rueckert, & N. Smith (Eds.), Functional Imaging and Modeling of the Heart: 7th International Conference, FIMH 2013, London, UK, June 20-22, 2013. Proceedings (224-231). Springer Verlag. https://doi.org/10.1007/978-3-642-38899-6_27

Experimental recordings of transmural activation in the human left ventricle show variability in recorded activation times. In this paper we demonstrate a framework for fitting the conductivity tensor of a monodomain model to reproduce activation tim... Read More about Estimation of Conductivity Tensors from Human Ventricular Optical Mapping Recordings.

Variability in high-throughput ion-channel screening data and consequences for cardiac safety assessment (2013)
Journal Article
Elkins, R. C., Davies, M. R., Brough, S. J., Gavaghan, D. J., Cui, Y., Abi-Gerges, N., & Mirams, G. R. (2013). Variability in high-throughput ion-channel screening data and consequences for cardiac safety assessment. Journal of Pharmacological and Toxicological Methods, 68(1), 112-122. https://doi.org/10.1016/j.vascn.2013.04.007

Introduction: Unwanted drug interactions with ionic currents in the heart can lead to an increased pro-arrhythmic risk to patients in the clinic. It is therefore a priority for safety pharmacology teams to detect block of cardiac ion channels, and ne... Read More about Variability in high-throughput ion-channel screening data and consequences for cardiac safety assessment.

Evaluation of an in silico cardiac safety assay: Using ion channel screening data to predict QT interval changes in the rabbit ventricular wedge (2013)
Journal Article
Beattie, K. A., Luscombe, C., Williams, G., Munoz-Muriedas, J., Gavaghan, D. J., Cui, Y., & Mirams, G. R. (2013). Evaluation of an in silico cardiac safety assay: Using ion channel screening data to predict QT interval changes in the rabbit ventricular wedge. Journal of Pharmacological and Toxicological Methods, 68(1), 88-96. https://doi.org/10.1016/j.vascn.2013.04.004

Introduction Drugs that prolong the QT interval on the electrocardiogram present a major safety concern for pharmaceutical companies and regulatory agencies. Despite a range of assays performed to assess compound effects on the QT interval, QT prolo... Read More about Evaluation of an in silico cardiac safety assay: Using ion channel screening data to predict QT interval changes in the rabbit ventricular wedge.

Chaste: An Open Source C++ Library for Computational Physiology and Biology (2013)
Journal Article
Mirams, G. R., Arthurs, C. J., Bernabeu, M. O., Bordas, R., Cooper, J., Corrias, A., …Gavaghan, D. J. (2013). Chaste: An Open Source C++ Library for Computational Physiology and Biology. PLoS Computational Biology, 9(3), e1002970. https://doi.org/10.1371/journal.pcbi.1002970

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac ele... Read More about Chaste: An Open Source C++ Library for Computational Physiology and Biology.

mRNA Expression Levels in Failing Human Hearts Predict Cellular Electrophysiological Remodeling: A Population-Based Simulation Study (2013)
Journal Article
Walmsley, J., Rodriguez, J. F., Mirams, G. R., Burrage, K., Efimov, I. R., & Rodriguez, B. (2013). mRNA Expression Levels in Failing Human Hearts Predict Cellular Electrophysiological Remodeling: A Population-Based Simulation Study. PLoS ONE, 8(2), https://doi.org/10.1371/journal.pone.0056359

Differences in mRNA expression levels have been observed in failing versus non-failing human hearts for several membrane channel proteins and accessory subunits. These differences may play a causal role in electrophysiological changes observed in hum... Read More about mRNA Expression Levels in Failing Human Hearts Predict Cellular Electrophysiological Remodeling: A Population-Based Simulation Study.

Computational assessment of drug-induced effects on the electrocardiogram: From ion channel to body surface potentials (2013)
Journal Article
Zemzemi, N., Bernabeu, M. O., Saiz, J., Cooper, J., Pathmanathan, P., Mirams, G. R., …Rodriguez, B. (2013). Computational assessment of drug-induced effects on the electrocardiogram: From ion channel to body surface potentials. British Journal of Pharmacology, 168(3), 718-733. https://doi.org/10.1111/j.1476-5381.2012.02200.x

Background and Purpose: Understanding drug effects on the heart is key to safety pharmacology assessment and anti-arrhythmic therapy development. Here our goal is to demonstrate the ability of computational models to simulate the effect of drug actio... Read More about Computational assessment of drug-induced effects on the electrocardiogram: From ion channel to body surface potentials.