Skip to main content

Research Repository

Advanced Search

All Outputs (129)

Resolving Artifacts in Voltage‐Clamp Experiments with Computational Modeling: An Application to Fast Sodium Current Recordings (2025)
Journal Article
Lok Lei, C., P. Clark, A., Clerx, M., Wei, S., Bloothooft, M., P. de Boer, T., J. Christini, D., Krogh‐Madsen, T., & R. Mirams, G. (2025). Resolving Artifacts in Voltage‐Clamp Experiments with Computational Modeling: An Application to Fast Sodium Current Recordings. Advanced Science, https://doi.org/10.1002/advs.202500691

Cellular electrophysiology underpins fields from basic science in neurology, cardiology, and oncology to safety critical applications for drug safety testing, risk assessment of rare mutations, and models based on cellular electrophysiology data even... Read More about Resolving Artifacts in Voltage‐Clamp Experiments with Computational Modeling: An Application to Fast Sodium Current Recordings.

Using Mathematical Models of Heart Cells to Assess the Safety of New Pharmaceutical Drugs (2025)
Book Chapter
Mirams, G. R. (2025). Using Mathematical Models of Heart Cells to Assess the Safety of New Pharmaceutical Drugs. In P. J. Aston (Ed.), More UK Success Stories in Industrial Mathematics (171-177). Springer. https://doi.org/10.1007/978-3-031-48683-8_22

Many drugs have been withdrawn from the market worldwide, at a cost of billions of dollars, because of patient fatalities due to drugs unexpectedly disturbing heart rhythm. Even drugs for ailments as mild as hay fever have been withdrawn due to an un... Read More about Using Mathematical Models of Heart Cells to Assess the Safety of New Pharmaceutical Drugs.

CRAC channel activity pulsates during cytosolic Ca2+ oscillations (2025)
Journal Article
Lin, Y.-P., Scappini, E., Mirams, G. R., Tucker, C. J., & Parekh, A. B. (2025). CRAC channel activity pulsates during cytosolic Ca2+ oscillations. Journal of Biological Chemistry, 301(6), Article 108519. https://doi.org/10.1016/j.jbc.2025.108519

Intracellular Ca2+ ions are used as second messengers throughout the phylogenetic tree. They are indispensable for diverse biological processes ranging from fertilization to cell death. In Metazoans, signaling information is conveyed via the amplitud... Read More about CRAC channel activity pulsates during cytosolic Ca2+ oscillations.

Modelling the effect of experimental conditions that influence rundown of L-type calcium current [version 1; peer review: awaiting peer review] (2025)
Preprint / Working Paper
Agrawal, A., Clerx, M., Wang, K., Polonchuk, L., R. Mirams, G., J. Gavaghan, D., Aditi, A., & David J., G. (2025). Modelling the effect of experimental conditions that influence rundown of L-type calcium current [version 1; peer review: awaiting peer review]

Background
L-type calcium channels (LCCs) are macro-molecular complexes that conduct ICaL and are involved in several critical functions in cardiac, skeletal, neuronal, smooth muscle, and endocrine cells. In common with other ionic channels they can... Read More about Modelling the effect of experimental conditions that influence rundown of L-type calcium current [version 1; peer review: awaiting peer review].

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.

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.

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.

Computational Cardiac Safety Testing (2024)
Book Chapter
Mirams, G. R. (2024). Computational Cardiac Safety Testing. In M. K. Pugsley, & F. J. Hock (Eds.), Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays (173-205). (Third Edition). Springer International Publishing. https://doi.org/10.1007/978-3-031-35529-5_137

In recent years, computational cardiac electrophysiology simulations using mathematical models have begun to be used in industrial and regulatory assessment of the proarrhythmic risk of candidate drug compounds. The aim of this chapter is to equip th... Read More about Computational Cardiac Safety Testing.

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, 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.

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.

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].