{"doi":"10.1085/jgp.202413582","title":"Modeling the effects of thin filament near-neighbor cooperative interactions in mammalian myocardium","abstract":"The mechanisms underlying cooperative activation and inactivation of myocardial force extend from local, near-neighbor interactions involving troponin-tropomyosin regulatory units (RU) and crossbridges (XB) to more global interactions across the sarcomere. To better understand these mechanisms in the hearts of small and large mammals, we undertook a simplified mathematical approach to assess the contribution of three types of near-neighbor cooperative interactions, i.e., RU-induced, RU-activation (RU-RU), crossbridge-induced, crossbridge-binding (XB-XB), and XB-induced, RU-activation (XB-RU). We measured the Ca2+ and activation dependence of the rate constant of force redevelopment in murine- and porcine-permeabilized ventricular myocardium. Mathematical modeling of these three near-neighbor interactions yielded nonlinear expressions for the RU-RU and XB-RU rate coefficients (kon and koff) and XB-XB rate coefficients describing the attachment of force-generating crossbridges (f and f'). The derivation of single cooperative coefficient parameters (u = RU-RU, w = XB-RU, and v = XB-XB) permitted an initial assessment of the strength of each near-neighbor interaction. The parameter sets describing the effects of discrete XB-XB or XB-RU interactions failed to adequately fit the in vitro contractility data in either murine or porcine myocardium. However, the Ca2+ dependence of ktr in murine and porcine ventricular myocardium was well fit by parameter sets incorporating the RU-RU cooperative interaction. Our results indicate that a significantly stronger RU-RU interaction is present in porcine ventricular myocardium compared with murine ventricular myocardium and that the relative strength of the near-neighbor RU-RU interaction contributes to species-specific myocardial contractile dynamics in small and large mammals.","journal":"The Journal of General Physiology","year":2024,"id":478255,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9455,"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":713198,"name":"Daniel P. Fitzsimons","orcid":"0000-0002-6833-7094","position":1,"is_corresponding":false},{"id":366448,"name":"Tuan Anh Phan","orcid":"0000-0002-4158-5493","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T02:06:42.155024Z","pmid":"39869069","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":[]}