Cardiomyocyte calcium handling in health and disease: Insights from in vitro and in silico studies. (November 2020)

• Record Type: Journal Article
• Authors: Sutanto, Henry; Lyon, Aurore; Lumens, Joost; Schotten, Ulrich; Dobrev, Dobromir; Heijman, Jordi
• Is Part Of: Progress in biophysics and molecular biology. Volume 157(2020)
• Page Start: 54
• Page End: 75
• Publication Date: 2020-11
• Subjects: Calcium handling -- Arrhythmia -- Computational modeling -- Cardiomyocyte -- Electrophysiology; Biophysics -- Periodicals; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular Biology -- Periodicals; Biophysique -- Périodiques; Biochimie -- Périodiques; 571.4
• DOI: 10.1016/j.pbiomolbio.2020.02.008
• Languages: English
• ISSNs: 0079-6107

Abstract

Abstract: Calcium (Ca 2+ ) plays a central role in cardiomyocyte excitation-contraction coupling. To ensure an optimal electrical impulse propagation and cardiac contraction, Ca 2+ levels are regulated by a variety of Ca 2+ -handling proteins. In turn, Ca 2+ modulates numerous electrophysiological processes. Accordingly, Ca 2+ -handling abnormalities can promote cardiac arrhythmias via various mechanisms, including the promotion of afterdepolarizations, ion-channel modulation and structural remodeling. In the last 30 years, significant improvements have been made in the computational modeling of cardiomyocyte Ca 2+ handling under physiological and pathological conditions. However, numerous questions involving the Ca 2+ -dependent regulation of different macromolecular complexes, cross-talk between Ca 2+ -dependent regulatory pathways operating over a wide range of time scales, and bidirectional interactions between electrophysiology and mechanics remain to be addressed by in vitro and in silico studies. A better understanding of disease-specific Ca 2+ -dependent proarrhythmic mechanisms may facilitate the development of improved therapeutic strategies. In this review, we describe the fundamental mechanisms of cardiomyocyte Ca 2+ handling in health and disease, and provide an overview of currently available computational models for cardiomyocyte Ca 2+ handling. Finally, we discuss important uncertainties and open questions about cardiomyocyte Ca 2+ handling and highlight how synergy between in vitro and in silico studies may help to answer several of these issues. Highlights: Ca 2+ -handling abnormalities play important roles in cardiac arrhythmogenesis. Computer models enable studies of cardiac electrophysiology in health and disease. Cardiomyocyte models can investigate complex Ca 2+ -dependent signaling pathways. Cardiomyocyte models provide insight in bidirectional electromechanical coupling. Interactions between in silico and in vitro studies may improve data accuracy.