Outputs (27)

Geometrically-derived action potential markers for model development: a principled approach? (2024)
Preprint / Working Paper
Clerx, M., & R Mirams, G. 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, 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)
Preprint / Working Paper
Agrawal, A., Clerx, M., Wang, K., Gissinger, E., J. Gavaghan, D., Polonchuk, L., & R. Mirams, G. An experimental investigation of rundown of the L-type calcium current [version 1; peer review: awaiting peer review]

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., G.A. Volders, P., & R. Mirams, G. 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., …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.

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.