{"doi":"10.3389/fphys.2021.730333","title":"Effects of TNFα on Dynamic Cytosolic Ca2 + and Force Responses to Muscarinic Stimulation in Airway Smooth Muscle","abstract":"Previously, we reported that in airway smooth muscle (ASM), the cytosolic Ca 2+ ([Ca 2+ ] cyt ) and force response induced by acetyl choline (ACh) are increased by exposure to the pro-inflammatory cytokine tumor necrosis factor α (TNFα). The increase in ASM force induced by TNFα was not associated with an increase in regulatory myosin light chain (rMLC 20 ) phosphorylation but was associated with an increase in contractile protein (actin and myosin) concentration and an enhancement of Ca 2+ dependent actin polymerization. The sensitivity of ASM force generation to elevated [Ca 2+ ] cyt (Ca 2+ sensitivity) is dynamic involving both the shorter-term canonical calmodulin-myosin light chain kinase (MLCK) signaling cascade that regulates rMLC 20 phosphorylation and cross-bridge recruitment as well as the longer-term regulation of actin polymerization that regulates contractile unit recruitment and actin tethering to the cortical cytoskeleton. In this study, we simultaneously measured [Ca 2+ ] cyt and force responses to ACh and explored the impact of 24-h TNFα on the dynamic relationship between [Ca 2+ ] cyt and force responses. The temporal delay between the onset of [Ca 2+ ] cyt and force responses was not affected by TNFα. Similarly, the rates of rise of [Ca 2+ ] cyt and force responses were not affected by TNFα. The absence of an impact of TNFα on the short delay relationships between [Ca 2+ ] cyt and force was consistent with the absence of an effect of [Ca 2+ ] cyt and force on rMLC 20 phosphorylation. However, the integral of the phase-loop plot of [Ca 2+ ] cyt and force increased with TNFα, consistent with an impact on actin polymerization and, contractile unit recruitment and actin tethering to the cortical cytoskeleton.","journal":"Frontiers in Physiology","year":2021,"id":208907,"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":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":313779,"name":"Philippe Delmotte","orcid":"0000-0003-1285-6554","position":1,"is_corresponding":false},{"id":313780,"name":"Gary C. Sieck","orcid":"0000-0003-3040-9424","position":2,"is_corresponding":false},{"id":796574,"name":"Young-Soo Han","orcid":null,"position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-18T23:52:01.526969Z","pmid":"34393833","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":[]}