Dr MICHAEL CLERX

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.

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].

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.

Geometrically-derived action potential markers for model development: a principled approach? (2024)
Preprint / Working Paper
Clerx, M., & Mirams, G. R. Geometrically-derived action potential markers for model development: a principled approach?

We explore whether action potential biomarkers can be rederived as functions of a linearisation of the action potential.

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.

Leak current, even with gigaohm seals, can cause misinterpretation of stem cell-derived cardiomyocyte action potential recordings (2023)
Journal Article
Clark, A. P., Clerx, M., Wei, S., Lei, C. L., de Boer, T. P., Mirams, G. R., Christini, D. J., & Krogh-Madsen, T. (2023). Leak current, even with gigaohm seals, can cause misinterpretation of stem cell-derived cardiomyocyte action potential recordings. EP-Europace, 25(9), Article euad243. https://doi.org/10.1093/europace/euad243

Aims
Human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have become an essential tool to study arrhythmia mechanisms. Much of the foundational work on these cells, as well as the computational models built from the resultant data,... Read More about Leak current, even with gigaohm seals, can cause misinterpretation of stem cell-derived cardiomyocyte action potential recordings.

Model-driven optimal experimental design for calibrating cardiac electrophysiology models (2023)
Journal Article
Lei, C. L., Clerx, M., Gavaghan, D. J., & Mirams, G. R. (2023). Model-driven optimal experimental design for calibrating cardiac electrophysiology models. Computer Methods and Programs in Biomedicine, 240, Article 107690. https://doi.org/10.1016/j.cmpb.2023.107690

Background and Objective: Models of the cardiomyocyte action potential have contributed immensely to the understanding of heart function, pathophysiology, and the origin of heart rhythm disturbances. However, action potential models are highly nonlin... Read More about Model-driven optimal experimental design for calibrating cardiac electrophysiology models.

Importance of modelling hERG binding in predicting drug-induced action potential prolongations for drug safety assessment (2023)
Journal Article
Farm, H. J., Clerx, M., Cooper, F., Polonchuk, L., Wang, K., Gavaghan, D. J., & Lei, C. L. (2023). Importance of modelling hERG binding in predicting drug-induced action potential prolongations for drug safety assessment. Frontiers in Pharmacology, 14, Article 1110555. https://doi.org/10.3389/fphar.2023.1110555

Reduction of the rapid delayed rectifier potassium current (IKr) via drug binding to the human Ether-à-go-go-Related Gene (hERG) channel is a well recognised mechanism that can contribute to an increased risk of Torsades de Pointes. Mathematical mode... Read More about Importance of modelling hERG binding in predicting drug-induced action potential prolongations for drug safety assessment.

Autocorrelated measurement processes and inference for ordinary differential equation models of biological systems (2023)
Journal Article
Lambert, B., Lei, C. L., Robinson, M., Clerx, M., Creswell, R., Ghosh, S., Tavener, S., & Gavaghan, D. J. (2023). Autocorrelated measurement processes and inference for ordinary differential equation models of biological systems. Journal of the Royal Society. Interface, 20(199), 20220725. https://doi.org/10.1098/rsif.2022.0725

Ordinary differential equation models are used to describe dynamic processes across biology. To perform likelihood-based parameter inference on these models, it is necessary to specify a statistical process representing the contribution of factors no... Read More about Autocorrelated measurement processes and inference for ordinary differential equation models of biological systems.

Normalisation of Action Potential Data Recorded with Sharp Electrodes Maximises Its Utility for Model Development (2022)
Presentation / Conference Contribution
Barral, Y. S. H., Polonchuk, L., R. Mirams, G., Clerx, M., Page, G., Sweat, K., Abi-Gerges, N., Wang, K., & Gavaghan, D. J. (2022, September). Normalisation of Action Potential Data Recorded with Sharp Electrodes Maximises Its Utility for Model Development. Presented at 2022 Computing in Cardiology Conference, Tampere, Finland

In silico models of cardiomyocyte electrophysiology describe the various ionic currents and fluxes that lead to the formation of action potentials (APs). Experimental data used to create such models can be recorded in adult human cardiac trabeculae u... Read More about Normalisation of Action Potential Data Recorded with Sharp Electrodes Maximises Its Utility for Model Development.

Modelling the Effect of Intracellular Calcium in the Rundown of L-Type Calcium Current (2022)
Presentation / Conference Contribution
Agrawal, A., Clerx, M., Wang, K., Polonchuk, L., Gavaghan, D. J., & Mirams, G. R. (2022, September). Modelling the Effect of Intracellular Calcium in the Rundown of L-Type Calcium Current. Presented at 2022 Computing in Cardiology Conference, Tampere, Finland

The L-type calcium current (ICaL) is a key current of the heart playing an important role in the contraction of the cardiomyocyte. Patch-clamp recordings of ionic currents can be associated with a reduction of the current magnitude with time (termed... Read More about Modelling the Effect of Intracellular Calcium in the Rundown of L-Type Calcium Current.

Derivative-based Inference for Cell and Channel Electrophysiology Models (2022)
Presentation / Conference Contribution
Clerx, M., Augustin, D., Dale-Evans, A. R., & Mirams, G. R. (2022, September). Derivative-based Inference for Cell and Channel Electrophysiology Models. Presented at 2022 Computing in Cardiology Conference, Tampere, Finland (online)

Models of ionic currents or of the cardiac action potential (AP) are frequently calibrated by defining an error function that quantifies the mismatch between simulations and data, and using numerical optimisation to find the parameter values that min... Read More about Derivative-based Inference for Cell and Channel Electrophysiology Models.

Models of the cardiac L-type calcium current: A quantitative review (2022)
Journal Article
Agrawal, A., Wang, K., Polonchuk, L., Cooper, J., Hendrix, M., Gavaghan, D. J., Gavaghan, D. J., Mirams, G. R., & Clerx, M. (2022). Models of the cardiac L-type calcium current: A quantitative review. Wiley Interdisciplinary Reviews: Mechanisms of Disease, 15(1), Article e1581. https://doi.org/10.1002/wsbm.1581

The L-type calcium current ((Formula presented.)) plays a critical role in cardiac electrophysiology, and models of (Formula presented.) are vital tools to predict arrhythmogenicity of drugs and mutations. Five decades of measuring and modeling (Form... Read More about Models of the cardiac L-type calcium current: A quantitative review.

cellmlmanip and chaste_codegen: automatic CellML to C++ code generation with fixes for singularities and automatically generated Jacobians (2022)
Journal Article
Hendrix, M., Clerx, M., Tamuri, A. U., Keating, S. M., Johnstone, R. H., Cooper, J., & Mirams, G. R. (2022). cellmlmanip and chaste_codegen: automatic CellML to C++ code generation with fixes for singularities and automatically generated Jacobians. Wellcome Open Research, 6, Article 261. https://doi.org/10.12688/wellcomeopenres.17206.2

Hundreds of different mathematical models have been proposed for describing electrophysiology of various cell types. These models are quite complex (nonlinear systems of typically tens of ODEs and sometimes hundreds of parameters) and software packag... Read More about cellmlmanip and chaste_codegen: automatic CellML to C++ code generation with fixes for singularities and automatically generated Jacobians.

A Parameter Representing Missing Charge Should Be Considered when Calibrating Action Potential Models (2022)
Journal Article
Barral, Y.-S. H. M., Shuttleworth, J., Clerx, M., Whittaker, D. G., Wang, K., Polonchuk, L., Gavaghan, D. J., & Mirams, G. R. (2022). A Parameter Representing Missing Charge Should Be Considered when Calibrating Action Potential Models. Frontiers in Physiology, 13, Article 879035. https://doi.org/10.3389/fphys.2022.879035

Computational models of the electrical potential across a cell membrane are longstanding and vital tools in electrophysiology research and applications. These models describe how ionic currents, internal fluxes, and buffering interact to determine me... Read More about A Parameter Representing Missing Charge Should Be Considered when Calibrating Action Potential Models.

Dr MICHAEL CLERX's Outputs (31)