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Professor GARY MIRAMS's Outputs (124)

Evaluating the predictive accuracy of ion-channel models using data from multiple experimental designs (2025)
Journal Article
Shuttleworth, J. G., Lei, C. L., Windley, M. J., Hill, A. P., Preston, S. P., & Mirams, G. R. (2025). Evaluating the predictive accuracy of ion-channel models using data from multiple experimental designs. Philosophical Transactions A: Mathematical, Physical and Engineering Sciences, 383(2292), Article 20240211. https://doi.org/10.1098/rsta.2024.0211

Mathematical models are increasingly being relied upon to provide quantitatively accurate predictions of cardiac electrophysiology. Many such models concern the behaviour of particular subcellular components (namely, ion channels) which, together, al... Read More about Evaluating the predictive accuracy of ion-channel models using data from multiple experimental designs.

Optimizing experimental designs for model selection of ion channel drug-binding mechanisms (2025)
Journal Article
Patten-Elliott, F., Lei, C. L., Preston, S. P., Wilkinson, R. D., & Mirams, G. R. (2025). Optimizing experimental designs for model selection of ion channel drug-binding mechanisms. Philosophical Transactions A: Mathematical, Physical and Engineering Sciences, 383(2292), https://doi.org/10.1098/rsta.2024.0227

The rapid delayed rectifier current carried by the human Ether-à-go-go-Related Gene (hERG) channel is susceptible to drug-induced reduction, which can lead to an increased risk of cardiac arrhythmia. Establishing the mechanism by which a specific dru... Read More about Optimizing experimental designs for model selection of ion channel drug-binding mechanisms.

Parameter inference for stochastic reaction models of ion channel gating from whole-cell voltage-clamp data (2025)
Journal Article
Del Core, L., & Mirams, G. R. (2025). Parameter inference for stochastic reaction models of ion channel gating from whole-cell voltage-clamp data. Philosophical Transactions A: Mathematical, Physical and Engineering Sciences, 383(2292), https://doi.org/10.1098/rsta.2024.0224

Mathematical models of ion channel gating describe the changes in ion channel configurations due to the electrical activity of the cell membrane. Experimental findings suggest that ion channels behave randomly, and therefore stochastic models of ion... Read More about Parameter inference for stochastic reaction models of ion channel gating from whole-cell voltage-clamp data.

Comparison of in silico predictions of action potential duration in response to inhibition of IKrand ICaLwith new human ex vivo recordings (2025)
Preprint / Working Paper
Barral, Y.-S. H., Polonchuk, L., Clerx, M., Gavaghan, D. J., Mirams, G. R., & Wang, K. Comparison of in silico predictions of action potential duration in response to inhibition of IKrand ICaLwith new human ex vivo recordings

During drug development, candidate compounds are extensively tested for proar-rhythmic risk and in particular risk of Torsade de Pointes (TdP), as indicated by prolongation of the QT interval. Drugs that inhibit the rapid delayed rectifier K+ current... Read More about Comparison of in silico predictions of action potential duration in response to inhibition of IKrand ICaLwith new human ex vivo recordings.

IonBench: a benchmark of optimisation strategies for mathematical models of ion channel currents (2025)
Preprint / Working Paper
Owen, M. J., & Mirams, G. R. IonBench: a benchmark of optimisation strategies for mathematical models of ion channel currents

Ion channel models present many challenging optimisation problems. These include unidentifiable parame- ters, noisy data, unobserved states, and a combination of both fast and slow timescales. This can make it difficult to choose a suitable optimisat... Read More about IonBench: a benchmark of optimisation strategies for mathematical models of ion channel currents.

A range of voltage-clamp protocol designs for rapid capture of hERG kinetics (2024)
Preprint / Working Paper
Lei, C. L., J Whittaker, D., J Windley, M., D Perry, M., P Hill, A., & R Mirams, G. A range of voltage-clamp protocol designs for rapid capture of hERG kinetics

We provide details of a series of short voltage-clamp protocols designed for gathering a large amount of information on hERG (Kv11.1) ion channel gating. The protocols have a limited number of steps and consist only of steps and ramps, making them ea... Read More about A range of voltage-clamp protocol designs for rapid capture of hERG kinetics.

Optimising experimental designs for model selection of ion channel drug binding mechanisms (2024)
Preprint / Working Paper
Patten-Elliott, F., Lei, C. L., Preston, S. P., Wilkinson, R. D., & Mirams, G. R. Optimising experimental designs for model selection of ion channel drug binding mechanisms

The rapid delayed rectifier current carried by the human Ether-à-go-go-Related Gene (hERG) channel is susceptible to drug-induced reduction which can lead to an increased risk of cardiac arrhythmia. Establishing the mechanism by which a specific drug... Read More about Optimising experimental designs for model selection of ion channel drug binding mechanisms.

Evaluating the predictive accuracy of ion channel models using data from multiple experimental designs (2024)
Preprint / Working Paper
Shuttleworth, J. G., Lei, C. L., Windley, M. J., Hill, A. P., Preston, S. P., & Mirams, G. R. Evaluating the predictive accuracy of ion channel models using data from multiple experimental designs

Mathematical models are increasingly being relied upon to provide quantitatively accurate predictions of cardiac electrophysiology. Many such models concern the behaviour of particular subcellular components (namely, ion channels) which, together, al... Read More about Evaluating the predictive accuracy of ion channel models using data from multiple experimental designs.

A range of voltage-clamp protocol designs for rapid capture of hERG kinetics (2024)
Preprint / Working Paper
Lei, C. L., Whittaker, D. G., Windley, M. J., Perry, M. D., Hill, A. P., & Mirams, G. R. A range of voltage-clamp protocol designs for rapid capture of hERG kinetics

We provide details of a series of short voltage-clamp protocols designed for gathering a large amount of information on hERG (Kv11.1) ion channel gating. The protocols have a limited number of steps and consist only of steps and ramps, making them ea... Read More about A range of voltage-clamp protocol designs for rapid capture of hERG kinetics.

Resolving artefacts in voltage-clamp experiments with computational modelling: an application to fast sodium current recordings. (2024)
Preprint / Working Paper
Lei, C. L., Clark, A. P., Clerx, M., Wei, S., Bloothooft, M., de Boer, T. P., Christini, D. J., Krogh-Madsen, T., & Mirams, G. R. Resolving artefacts in voltage-clamp experiments with computational modelling: an application to fast sodium current recordings

Cellular electrophysiology is the foundation of many fields, from basic science in neurology, cardiology, oncology to safety critical applications for drug safety testing, clinical phenotyping, etc. Patch-clamp voltage clamp is the gold standard tech... Read More about Resolving artefacts in voltage-clamp experiments with computational modelling: an application to fast sodium current recordings..

Optimal experimental designs for characterising ion channel gating by filling the phase-voltage space of model dynamics (2024)
Journal Article
Mirams, G. R., Clerx, M., Whittaker, D. G., & Lei, C. L. (2024). Optimal experimental designs for characterising ion channel gating by filling the phase-voltage space of model dynamics. Mathematics in Medical and Life Sciences, 2024(1), Article 2375494. https://doi.org/10.1080/29937574.2024.2375494

Voltage-clamp waveforms are imposed in the patch-clamp electrophysiology technique to provoke ion currents, the particular waveform that is used is known as the “voltage-clamp protocol”. Designing protocols to probe and quantify how gating for a part... Read More about Optimal experimental designs for characterising ion channel gating by filling the phase-voltage space of model dynamics.

Optimal experimental designs for characterising ion channel gating by filling the phase-voltage space of model dynamics (2024)
Journal Article
Mirams, G. R., Clerx, M., Whittaker, D. G., & Lei, C. L. (2024). Optimal experimental designs for characterising ion channel gating by filling the phase-voltage space of model dynamics. Mathematics in Medical and Life Sciences, 1(1), Article 2375494. https://doi.org/10.1080/29937574.2024.2375494

Voltage-clamp waveforms are imposed in the patch-clamp electrophysiology technique to provoke ion currents, the particular waveform that is used is known as the “voltage-clamp protocol”. Designing protocols to probe and quantify how gating for a part... Read More about Optimal experimental designs for characterising ion channel gating by filling the phase-voltage space of model dynamics.

An experimental investigation of rundown of the L-type calcium current [version 1; peer review: awaiting peer review] (2024)
Journal Article
Agrawal, A., Clerx, M., Wang, K., Gissinger, E., Gavaghan, D. J., Polonchuk, L., & Mirams, G. R. (in press). An experimental investigation of rundown of the L-type calcium current [version 1; peer review: awaiting peer review]. Wellcome Open Research, 9, 250. https://doi.org/10.12688/wellcomeopenres.20374.1

Background

L-type calcium channels (LCCs) are multi-protein macro-molecular ion channel complexes that are involved in several critical functions in cardiac, skeletal, neuronal, smooth muscle, and endocrine cells. Like other ion channels, LCCs can... Read More about An experimental investigation of rundown of the L-type calcium current [version 1; peer review: awaiting peer review].

Variability in reported midpoints of (in)activation of cardiac INa (2024)
Preprint / Working Paper
Clerx, M., Volders, P. G., & Mirams, G. R. Variability in reported midpoints of (in)activation of cardiac INa

Electrically active cells like cardiomyocytes show variability in their size, shape, and electrical activity. But should we expect variability in the properties of their ionic currents? In this brief review we gather and visualise measurements of two... Read More about Variability in reported midpoints of (in)activation of cardiac INa.

Neural network emulation of the human ventricular cardiomyocyte action potential for more efficient computations in pharmacological studies (2024)
Journal Article
Grandits, T., Augustin, C. M., Haase, G., Jost, N., Mirams, G. R., Niederer, S. A., Plank, G., Varró, A., Virág, L., & Jung, A. (2024). Neural network emulation of the human ventricular cardiomyocyte action potential for more efficient computations in pharmacological studies. eLife, 12, Article RP91911. https://doi.org/10.7554/elife.91911.3

Computer models of the human ventricular cardiomyocyte action potential (AP) have reached a level of detail and maturity that has led to an increasing number of applications in the pharmaceutical sector. However, interfacing the models with experimen... Read More about Neural network emulation of the human ventricular cardiomyocyte action potential for more efficient computations in pharmacological studies.

Compartmentalization proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation (2024)
Journal Article
Ayagama, T., Charles, P. D., Bose, S. J., Boland, B., Priestman, D. A., Aston, D., Berridge, G., Fisher, R., Cribbs, A. P., Song, Q., Mirams, G. R., Amponsah, K., Heather, L., Galione, A., Herring, N., Kramer, H., Capel, R. A., Platt, F. M., Schotten, U., Verheule, S., & Burton, R. A. (2024). Compartmentalization proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation. iScience, 27(6), Article 109609. https://doi.org/10.1016/j.isci.2024.109609

Endolysosomes (EL) are known for their role in regulating both intracellular trafficking and proteostasis. EL facilitate the elimination of damaged membranes, protein aggregates, membranous organelles and play an important role in calcium signaling.... Read More about Compartmentalization proteomics revealed endolysosomal protein network changes in a goat model of atrial fibrillation.

Understanding the impact of numerical solvers on inference for differential equation models (2024)
Journal Article
Creswell, R., Shepherd, K. M., Lambert, B., Mirams, G. R., Lei, C. L., Tavener, S., Robinson, M., & Gavaghan, D. J. (2024). Understanding the impact of numerical solvers on inference for differential equation models. Journal of the Royal Society, Interface, 21(212), Article 20230369. https://doi.org/10.1098/rsif.2023.0369

Most ordinary differential equation (ODE) models used to describe biological or physical systems must be solved approximately using numerical methods. Perniciously, even those solvers that seem sufficiently accurate for the forward problem, i.e. for... Read More about Understanding the impact of numerical solvers on inference for differential equation models.

Strengthening cardiac therapy pipelines using human pluripotent stem cell-derived cardiomyocytes (2024)
Journal Article
Raniga, K., Nasir, A., Vo, N. T., Vaidyanathan, R., Dickerson, S., Hilcove, S., Mosqueira, D., Mirams, G. R., Clements, P., Hicks, R., Pointon, A., Stebbeds, W., Francis, J., & Denning, C. (2024). Strengthening cardiac therapy pipelines using human pluripotent stem cell-derived cardiomyocytes. Cell Stem Cell, 31(3), 292-311. https://doi.org/10.1016/j.stem.2024.01.007

Advances in hiPSC isolation and reprogramming and hPSC-CM differentiation have prompted their therapeutic application and utilization for evaluating potential cardiovascular safety liabilities. In this perspective, we showcase key efforts toward the... Read More about Strengthening cardiac therapy pipelines using human pluripotent stem cell-derived cardiomyocytes.