Calcium buffers and L-type calcium channels as modulators of cardiac subcellular alternans

Lai, Yi Ming; Coombes, Stephen; Thul, R�diger

Abstract

In cardiac myocytes, calcium cycling links the dynamics of the membrane potential to the activation of the contractile filaments. Perturbations of the calcium signalling toolkit have been demonstrated to disrupt this connection and lead to numerous pathologies including cardiac alternans. This rhythm disturbance is characterised by alternations in the membrane potential and the intracellular calcium concentration, which in turn can lead to sudden cardiac death. In the present computational study, we make further inroads into understanding this severe condition by investigating the impact of calcium buffers and L-type calcium channels on the formation of subcellular calcium alternans when calcium diffusion in the cytosol is weak and the main route of transport in the myocyte is via the sarcoplasmic reticulum. Through numerical simulations of a two dimensional network of calcium release units, we show that increasing calcium entry is proarrhythmogenic and that this is modulated by the calcium-dependent inactivation of the L-type calcium channel. We also find that while calcium buffers can exert a stabilising force and abolish subcellular alternans, they can significantly shape the spatial patterning of subcellular calcium alternans. Taken together, our results demonstrate that subcellular calcium alternans can emerge via various routes and that calcium diffusion in the sarcoplasmic reticulum critically determines their spatial patterns.

Citation

Lai, Y. M., Coombes, S., & Thul, R. (2020). Calcium buffers and L-type calcium channels as modulators of cardiac subcellular alternans. Communications in Nonlinear Science and Numerical Simulation, 85, Article 105181. https://doi.org/10.1016/j.cnsns.2020.105181

• Journal Article Type: Article
• Acceptance Date: Jan 8, 2020
• Online Publication Date: Feb 21, 2020
• Publication Date: 2020-06
• Deposit Date: Jun 7, 2022
• Publicly Available Date: Jun 7, 2022
• Journal: Communications in Nonlinear Science and Numerical Simulation
• Print ISSN: 1007-5704
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 85
• Article Number: 105181
• DOI: https://doi.org/10.1016/j.cnsns.2020.105181
• Keywords: Modelling and Simulation; Applied Mathematics; Numerical Analysis
• Public URL: https://nottingham-repository.worktribe.com/output/3971033
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S1007570420300162?via%3Dihub