{"doi":"10.1016/j.bpr.2024.100183","title":"Expression level of cardiac ryanodine receptors dictates properties of Ca2+-induced Ca2+ release","abstract":"The type 2 ryanodine receptor (RyR2) is the major Ca 2+ release channel required for Ca 2+ -induced Ca 2+ release (CICR) and cardiac excitation-contraction coupling. The cluster organization of RyR2 at the dyad is critical for efficient CICR. Despite its central role in cardiac Ca 2+ signaling, the mechanisms that control CICR are not fully understood. As a single RyR2 Ca 2+ flux dictates local CICR that underlies Ca 2+ sparks, RyR2 density in a cluster, and therefore the distance between RyR2s, should have a profound impact on local CICR. Here, we studied the effect of the RyR2 expression level ([RyR2]) on CICR activation, termination, and amplitude. The endoplasmic reticulum (ER)-targeted Ca 2+ sensor RCEPIA-1er was used to directly measure the ER [Ca 2+ ] (Ca 2+ ] ER ) in the T-Rex-293 the sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA2a) stable cell line expressing human RyR2. Cells coexpressing RyR2 and SERCA2a produced periodic [Ca 2+ ] ER depletions in the form of spontaneous Ca 2+ waves due to propagating CICR. For each studied cell, the [Ca 2+ ] ER at which Ca 2+ waves are activated and terminated was analyzed as a function of [RyR2]. CICR parameters, such as [Ca 2+ ] ER activation, termination, and amplitude, were inversely proportional to [RyR2] at low-intermediate levels. Increasing the sensitivity of RyR2 to cytosolic Ca 2+ lowered the [Ca 2+ ] ER at which CICR is activated and terminated. Decreasing the sensitivity of RyR2 to cytosolic Ca 2+ had the opposite effect on CICR. These results suggest that RyR2 density in the release cluster should have a significant impact on local CICR activation and termination. Since SR Ca 2+ load is evenly distributed throughout the SR network, clusters with higher RyR2 density would have a higher probability of initiating spontaneous CICR.","journal":"Biophysical Reports","year":2024,"id":469306,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9473,"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":406898,"name":"Elisa Bovo","orcid":"0000-0002-9709-6381","position":1,"is_corresponding":false},{"id":406904,"name":"Aleksey V. Zima","orcid":"0000-0001-7280-2924","position":2,"is_corresponding":false},{"id":406899,"name":"Roman Nikolaienko","orcid":"0000-0002-9836-2880","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-19T02:05:28.027781Z","pmid":"39341600","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":[]}