All Outputs (8)

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Many drugs have been withdrawn from the market worldwide, at a cost of billions of dollars, because of patient fatalities due to drugs unexpectedly disturbing heart rhythm. Even drugs for ailments as mild as hay fever have been withdrawn due to an un...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].

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.

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.

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.