Cardiomyocyte calcium handling in health and disease: Insights from in vitro and in silico studies

Henry Sutanto, Aurore Lyon, Joost Lumens, Ulrich Schotten, Dobromir Dobrev, Jordi Heijman*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

34 Citations (Web of Science)

Abstract

Calcium (Ca2þ) plays a central role in cardiomyocyte excitation-contraction coupling. To ensure an optimal electrical impulse propagation and cardiac contraction, Ca2þ levels are regulated by a variety of Ca2þ-handling proteins. In turn, Ca2þ modulates numerous electrophysiological processes. Accordingly, Ca2þ-handling abnormalities can promote cardiac arrhythmias via various mechanisms, including the promotion of after depolarizations, ion-channel modulation and structural remodeling. In the last 30 years, significant improvements have been made in the computational modeling of cardiomyocyte Ca2þ-handling under physiological and pathological conditions. However, numerous questions involving the Ca2þ-dependent regulation of different macromolecular complexes, cross-talk between Ca2þ-dependentregulatory pathways operating over a wide range of time scales, and bidirectional interactions between electro physiology and mechanics remain to be addressed by in vitro and in silico studies. A better understanding of disease-specific Ca2þ-dependent proarrhythmic mechanisms may facilitate the development of improved therapeutic strategies. In this review, we describe the fundamental mechanisms of cardiomyocyte Ca2þ-handling in health and disease, and provide an overview of currently available computational models for cardiomyocyte Ca2þ-handling. Finally, we discuss important uncertainties and open questions about cardiomyocyte Ca2þhandling and highlight how synergy between in vitro and
in silico studies may help to answer several of these issues.
Original languageEnglish
Pages (from-to)54-75
Number of pages22
JournalProgress in Biophysics & Molecular Biology
Volume157
DOIs
Publication statusPublished - Nov 2020

Keywords

  • Calcium handling
  • Arrhythmia
  • Computational modeling
  • Cardiomyocyte
  • Electrophysiology
  • SARCOPLASMIC-RETICULUM CA2+
  • PROTEIN-KINASE-II
  • ACTIVATED POTASSIUM CHANNELS
  • ATRIAL-FIBRILLATION
  • INTRACELLULAR CALCIUM
  • VENTRICULAR MYOCYTES
  • DEPENDENT REGULATION
  • HEART-FAILURE
  • RYR2 PHOSPHORYLATION
  • MECHANOELECTRICAL FEEDBACK

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