{"doi":"10.1016/j.pbiomolbio.2020.02.008","title":"Cardiomyocyte calcium handling in health and disease: Insights from in vitro and in silico studies","abstract":"Calcium (Ca2+) plays a central role in cardiomyocyte excitation-contraction coupling. To ensure an optimal electrical impulse propagation and cardiac contraction, Ca2+ levels are regulated by a variety of Ca2+-handling proteins. In turn, Ca2+ modulates numerous electrophysiological processes. Accordingly, Ca2+-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 Ca2+ handling under physiological and pathological conditions. However, numerous questions involving the Ca2+-dependent regulation of different macromolecular complexes, cross-talk between Ca2+-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 Ca2+-dependent proarrhythmic mechanisms may facilitate the development of improved therapeutic strategies. In this review, we describe the fundamental mechanisms of cardiomyocyte Ca2+ handling in health and disease, and provide an overview of currently available computational models for cardiomyocyte Ca2+ handling. Finally, we discuss important uncertainties and open questions about cardiomyocyte Ca2+ handling and highlight how synergy between in vitro and in silico studies may help to answer several of these issues.","journal":"Progress in Biophysics and Molecular Biology","year":2020,"id":53088,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":122,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9532,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":270326,"name":"Aurore Lyon","orcid":"0000-0001-6019-7376","position":1,"is_corresponding":false},{"id":270327,"name":"Joost Lumens","orcid":"0000-0001-8129-7384","position":2,"is_corresponding":false},{"id":58206,"name":"Ulrich Schotten","orcid":"0000-0003-1532-3315","position":3,"is_corresponding":false},{"id":58218,"name":"Dobromir Dobrev","orcid":"0000-0002-4612-117X","position":4,"is_corresponding":false},{"id":270328,"name":"Jordi Heijman","orcid":"0000-0002-1418-108X","position":5,"is_corresponding":false},{"id":270325,"name":"Henry Sutanto","orcid":"0000-0002-5730-2013","position":0,"is_corresponding":true}],"reference_count":288,"raw_metadata":null,"created_at":"2026-07-18T20:44:25.349797Z","pmid":"32188566","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}