Models of the cardiac L-type calcium current: A quantitative review

Agrawal, Aditi; Wang, Ken; Polonchuk, Liudmila; Cooper, Jonathan; Hendrix, Maurice; Gavaghan, David J; Gavaghan, David J.; Mirams, Gary R.; Clerx, Michael

Abstract

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 (Formula presented.) have resulted in several competing theories (encoded in mathematical equations). However, the introduction of new models has not typically been accompanied by a data-driven critical comparison with previous work, so that it is unclear which model is best suited for any particular application. In this review, we describe and compare 73 published mammalian (Formula presented.) models and use simulated experiments to show that there is a large variability in their predictions, which is not substantially diminished when grouping by species or other categories. We provide model code for 60 models, list major data sources, and discuss experimental and modeling work that will be required to reduce this huge list of competing theories and ultimately develop a community consensus model of (Formula presented.). This article is categorized under: Cardiovascular Diseases > Computational Models Cardiovascular Diseases > Molecular and Cellular Physiology.

Citation

Agrawal, A., Wang, K., Polonchuk, L., Cooper, J., Hendrix, M., Gavaghan, D. J., …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

• Journal Article Type: Review
• Acceptance Date: Jul 19, 2022
• Online Publication Date: Aug 26, 2022
• Publication Date: Aug 26, 2022
• Deposit Date: Jul 28, 2022
• Publicly Available Date: Aug 26, 2022
• Journal: Wiley Interdisciplinary Reviews: Mechanisms of Disease
• Electronic ISSN: 2692-9368
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 1
• Article Number: e1581
• DOI: https://doi.org/10.1002/wsbm.1581
• Keywords: Computational Models, Molecular and Cellular Physiology, Advanced Review, Advanced Reviews, calcium channel, cellular electrophysiology, computational model, L‐type calcium current
• Public URL: https://nottingham-repository.worktribe.com/output/9408031
• Publisher URL: https://wires.onlinelibrary.wiley.com/doi/10.1002/wsbm.1581