{"doi":"10.3389/fphys.2024.1479882","title":"Long-term hypoxia modulates depolarization activation of BKCa currents in fetal sheep middle cerebral arterial myocytes","abstract":"Introduction Previous evidence indicates that gestational hypoxia disrupts cerebrovascular development, increasing the risk of intracranial hemorrhage and stroke in the newborn. Due to the role of cytosolic Ca 2+ in regulating vascular smooth muscle (VSM) tone and fetal cerebrovascular blood flow, understanding Ca 2+ signals can offer insight into the pathophysiological disruptions taking place in hypoxia-related perinatal cerebrovascular disease. This study aimed to determine the extent to which gestational hypoxia disrupts local Ca 2+ sparks and whole-cell Ca 2+ signals and coupling with BK Ca channel activity. Methods Confocal imaging of cytosolic Ca 2+ and recording BK Ca currents of fetal sheep middle cerebral arterial (MCA) myocytes was performed. MCAs were isolated from term fetal sheep (∼140 days of gestation) from ewes held at low- (700 m) and high-altitude (3,801 m) hypoxia (LTH) for 100+ days of gestation. Arteries were depolarized with 30 mM KCl (30K), in the presence or absence of 10 μM ryanodine (Ry), to block RyR mediated Ca 2+ release. Results Membrane depolarization increased Ry-sensitive Ca 2+ spark frequency in normoxic and LTH groups along with BK Ca activity. LTH reduced Ca 2+ spark and whole-cell Ca 2+ activity and induced a large leftward shift in the voltage-dependence of BK Ca current activation. The influence of LTH on the spatial and temporal aspects of Ca 2+ sparks and whole-cell Ca 2+ responses varied. Discussion Overall, LTH attenuates Ca 2+ signaling while increasing the coupling of Ca 2+ sparks to BK Ca activity; a process that potentially helps maintain oxygen delivery to the developing brain.","journal":"Frontiers in Physiology","year":2024,"id":505761,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"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":1157885,"name":"Madison Boskind","orcid":null,"position":1,"is_corresponding":false},{"id":402491,"name":"Xiang‐Qun Hu","orcid":"0000-0003-1626-9541","position":2,"is_corresponding":false},{"id":1356905,"name":"David Mallari","orcid":null,"position":3,"is_corresponding":false},{"id":493973,"name":"Michelle Chan","orcid":"0000-0001-6037-7051","position":4,"is_corresponding":false},{"id":1356906,"name":"Devin Wilson","orcid":null,"position":5,"is_corresponding":false},{"id":403533,"name":"Monica Romero","orcid":null,"position":6,"is_corresponding":false},{"id":1356907,"name":"Eris Albert-Minckler","orcid":null,"position":7,"is_corresponding":false},{"id":291057,"name":"Li Zhang","orcid":"0000-0002-9386-8938","position":8,"is_corresponding":false},{"id":921866,"name":"Arlin B. Blood","orcid":"0000-0002-4803-5021","position":9,"is_corresponding":false},{"id":834152,"name":"Christopher G. Wilson","orcid":"0000-0003-4644-5593","position":10,"is_corresponding":false},{"id":913711,"name":"Jośe L. Puglisi","orcid":"0000-0003-0241-8446","position":11,"is_corresponding":false},{"id":402493,"name":"Sean M. Wilson","orcid":"0000-0003-4404-1173","position":12,"is_corresponding":false},{"id":1157886,"name":"Nikitha Nelapudi","orcid":null,"position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T02:10:47.170978Z","pmid":"39563935","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":[]}