{"doi":"10.1085/jgp.202413545","title":"Calcium has a direct effect on thick filament activation in porcine myocardium","abstract":"Sarcomere activation in striated muscle requires both thin filament-based and thick filament-based activation mechanisms. Recent studies have shown that myosin heads on the thick filaments undergo OFF to ON structural transitions in response to calcium (Ca2+) in permeabilized porcine myocardium in the presence of a small molecule inhibitor that eliminated active force. The changes in X-ray diffraction signatures of OFF to ON transitions were interpreted as Ca2+ acting to activate the thick filaments. Alternatively, Ca2+ binding to troponin could initiate a Ca2+-dependent crosstalk from the thin filament to the thick filament via interfilament connections such as the myosin binding protein-C. Here, we exchanged native troponin in permeabilized porcine myocardium for troponin containing the cTnC D65A mutation, which disallows the activation of troponin through Ca2+ binding to determine if Ca2+-dependent thick filament activation persists in the absence of thin filament activation. After the exchange protocol, over 95% of the Ca2+-activated force was eliminated. Equatorial intensity ratio increased significantly in both WT and D65A exchanged myocardium with increasing Ca2+ concentration. The degree of helical ordering of the myosin heads decreased by the same amount in WT and D65A myocardium when Ca2+ concentration increased. These results are consistent with a direct effect of Ca2+ in activating the thick filament rather than an indirect effect due to Ca2+-mediated crosstalk between the thick and thin filaments.","journal":"The Journal of General Physiology","year":2024,"id":441165,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":400434,"name":"Timothy S. McMillen","orcid":"0000-0001-5261-3229","position":1,"is_corresponding":false},{"id":301608,"name":"Christian Mandrycky","orcid":"0000-0002-6564-7265","position":2,"is_corresponding":false},{"id":953802,"name":"An-Yue Tu","orcid":null,"position":3,"is_corresponding":false},{"id":476801,"name":"Kristina B. Kooiker","orcid":"0000-0003-1817-9080","position":4,"is_corresponding":false},{"id":916407,"name":"Wenjing Qian","orcid":"0000-0003-0236-5639","position":5,"is_corresponding":false},{"id":1253598,"name":"Stephanie Neys","orcid":"0009-0007-3455-9370","position":6,"is_corresponding":false},{"id":1253599,"name":"Brayan Osegueda","orcid":"0000-0002-9281-8357","position":7,"is_corresponding":false},{"id":472057,"name":"Farid Moussavi‐Harami","orcid":"0000-0002-0189-7214","position":8,"is_corresponding":false},{"id":355536,"name":"Thomas C. Irving","orcid":"0000-0003-4848-3323","position":9,"is_corresponding":false},{"id":347667,"name":"Michael Regnier","orcid":"0000-0001-5437-9851","position":10,"is_corresponding":false},{"id":355530,"name":"Weikang Ma","orcid":"0000-0001-9535-7114","position":11,"is_corresponding":false},{"id":1031799,"name":"Saffie Mohran","orcid":"0000-0003-0728-9882","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T02:01:06.281460Z","pmid":"39302315","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":[]}