{"doi":"10.1111/apha.14208","title":"Mitochondria can substitute for parvalbumin to lower cytosolic calcium levels in the murine fast skeletal muscle","abstract":"Abstract Aim Parvalbumin (PV) is a primary calcium buffer in mouse fast skeletal muscle fibers. Previous work showed that PV ablation has a limited impact on cytosolic Ca 2+ ([Ca 2+ ] cyto ) transients and contractile response, while it enhances mitochondrial density and mitochondrial matrix‐free calcium concentration ([Ca 2+ ] mito ). Here, we aimed to quantitatively test the hypothesis that mitochondria act to compensate for PV deficiency. Methods We determined the free Ca 2+ redistribution during a 2 s 60 Hz tetanic stimulation in the sarcoplasmic reticulum, cytosol, and mitochondria. Via a reaction–diffusion Ca 2+ model, we quantitatively evaluated mitochondrial uptake and storage capacity requirements to compensate for PV lack and analyzed possible extracellular export. Results [Ca 2+ ] mito during tetanic stimulation is greater in knock‐out (KO) (1362 ± 392 nM) than in wild‐type (WT) (855 ± 392 nM), p < 0.05. Under the assumption of a non‐linear intramitochondrial buffering, the model predicts an accumulation of 725 μmoles/ L fiber (buffering ratio 1:11 000) in KO, much higher than in WT (137 μmoles/ L fiber , ratio 1:4500). The required transport rate via mitochondrial calcium uniporter (MCU) reaches 3 mM/s, compatible with available literature. TEM images of calcium entry units and Mn 2+ quenching showed a greater capacity of store‐operated calcium entry in KO compared to WT. However, levels of [Ca 2+ ] cyto during tetanic stimulation were not modulated to variations of extracellular calcium. Conclusions The model‐based analysis of experimentally determined calcium distribution during tetanic stimulation showed that mitochondria can act as a buffer to compensate for the lack of PV. This result contributes to a better understanding of mitochondria's role in modulating [Ca 2+ ] cyto in skeletal muscle fibers.","journal":"Acta Physiologica","year":2024,"id":445179,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"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":999843,"name":"Leonardo Nogara","orcid":"0000-0002-7009-8707","position":1,"is_corresponding":false},{"id":1000100,"name":"Marta Canato","orcid":null,"position":2,"is_corresponding":false},{"id":1261090,"name":"Elena Germinario","orcid":"0000-0003-1312-7476","position":3,"is_corresponding":false},{"id":999848,"name":"Anna Raffaello","orcid":"0000-0002-8344-6459","position":4,"is_corresponding":false},{"id":1261091,"name":"Michela Carraro","orcid":"0000-0002-4573-9306","position":5,"is_corresponding":false},{"id":542901,"name":"Paolo Bernardi","orcid":"0000-0001-9187-3736","position":6,"is_corresponding":false},{"id":456811,"name":"Laura Pietrangelo","orcid":"0000-0003-1197-7813","position":7,"is_corresponding":false},{"id":456810,"name":"Simona Boncompagni","orcid":"0000-0001-5308-5069","position":8,"is_corresponding":false},{"id":456813,"name":"Feliciano Protasi","orcid":"0000-0002-0213-7591","position":9,"is_corresponding":false},{"id":383581,"name":"Nazareno Paolocci","orcid":"0000-0001-7011-997X","position":10,"is_corresponding":false},{"id":1261092,"name":"Carlo Reggiani","orcid":"0000-0001-8080-361X","position":11,"is_corresponding":false},{"id":999845,"name":"Lorenzo Marcucci","orcid":"0000-0002-9542-4417","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T02:01:42.089235Z","pmid":"39077881","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":[]}