{"doi":"10.33549/physiolres.931875","title":"A role for receptor-operated Ca2+ entry in human pulmonary artery smooth muscle cells in response to hypoxia","abstract":"<jats:p>Hypoxic pulmonary vasoconstriction (HPV) is an important\nhomeostatic mechanism in which increases of [Ca2+]i are primary\nevents. In this study, primary cultured, human pulmonary artery\nsmooth muscle cells (hPASMC) were used to examine the role of\nTRPC channels in mediating [Ca2+]i elevations during hypoxia.\nHypoxia (PO2 about 20 mm Hg) evoked a transient [Ca2+]i elevation\nthat was reduced by removal of extracellular calcium. Nifedipine\nand verapamil, blockers of voltage-gated calcium channels\n(VGCCs), attenuated the hypoxia-induced [Ca2+]i elevation by\nabout 30 %, suggesting the presence of alternate Ca2+ entry\npathways. Expression of TRPC1 and TRPC6 in hPASMC were found\nby RT-PCR and confirmed by Western blot analysis. Antagonists for\nTRPC, 2APB and SKF96365, significantly reduced hypoxia-induced\n[Ca2+]i elevation by almost 60 %. Both TRPC6 and TRPC1 were\nknocked down by siRNA, the loss of TRPC6 decreased hypoxic\nresponse down to 21 % of control, whereas the knockdown of\nTRPC1 reduced the hypoxia response to 85 %, suggesting that\nTRPC6 might play a central role in mediating hypoxia response in\nhPASMC. However, blockade of PLC pathway caused only small\ninhibition of the hypoxia response. In contrast, AICAR, the agonist\nof AMP-activated kinase (AMPK), induced a gradual [Ca2+]i\nelevation, whereas compound C, an antagonist of AMPK, almost\nabolished the hypoxia response. However, co-immunoprecipitation\nrevealed that AMPKα was not colocalized with TRPC6. Our data\nsupports a role for TRPC6 in mediation of the [Ca2+]i elevation in\nresponse to hypoxia in hPASMC and suggests that this response\nmay be linked to cellular energy status via an activation of AMPK.</jats:p>","journal":"Physiological Research","year":2010,"id":26128,"datarank":1.7225417688822162,"base_score":3.58351893845611,"endowment":3.58351893845611,"self_citation_contribution":0.5375278407684165,"citation_network_contribution":1.1850139281137997,"self_endowment_contribution":0.5375278407684165,"citer_contribution":1.1850139281137997,"corpus_percentile":null,"corpus_rank":null,"citation_count":35,"citer_count":34,"citers_with_citation_signal":32,"citers_with_endowment":32,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":151874,"name":"WK To","orcid":null,"position":1,"is_corresponding":false},{"id":151875,"name":"F Meng","orcid":null,"position":2,"is_corresponding":false},{"id":151876,"name":"Y Wang","orcid":null,"position":3,"is_corresponding":false},{"id":151877,"name":"Y Gu","orcid":null,"position":4,"is_corresponding":false},{"id":151873,"name":"C Tang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.58351893845611,"endowment":3.58351893845611,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"20533864","pmcid":null,"openalex_id":"https://openalex.org/W2122870745","authors":[],"funders":[{"funder_name":"British Heart Foundation","grant_id":"","title":null},{"funder_name":"British Heart Foundation","grant_id":"","title":null}],"total_grants":2,"fwci":1.9831,"citation_percentile":0.84883721,"influential_citations":0,"citation_trend":[{"year":2012,"count":8},{"year":2013,"count":4},{"year":2014,"count":3},{"year":2015,"count":6},{"year":2016,"count":1},{"year":2017,"count":2},{"year":2018,"count":2},{"year":2019,"count":3},{"year":2020,"count":1},{"year":2023,"count":1},{"year":2024,"count":1},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://doi.org/10.33549/physiolres.931875","host_type":"journal"},{"url":"https://doi.org/10.33549/physiolres.931875","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/20533864","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.188.2759","host_type":""},{"url":"https://research.birmingham.ac.uk/en/publications/38f3e482-7a87-443e-b6af-b8b4eb1fbd9e","host_type":"repository"}],"fields_of_study":["Ion Channels and Receptors","Ion channel regulation and function","Neuroscience of respiration and sleep","AMP-Activated Protein Kinases","Calcium","Calcium Channels","Cell Hypoxia","Cells, Cultured","Humans","Muscle, Smooth, Vascular","Myocytes, Smooth Muscle","Pulmonary Artery","RNA, Small Interfering","Reverse Transcriptase Polymerase Chain Reaction","TRPC Cation Channels","TRPC6 Cation Channel"],"mesh_terms":["TRPC6 Cation Channel","Calcium","Cells, Cultured","Humans","Muscle, Smooth, Vascular","Pulmonary Artery","Calcium Channels","Cell Hypoxia","Reverse Transcriptase Polymerase Chain Reaction","Myocytes, Smooth Muscle","RNA, Small Interfering","TRPC Cation Channels","AMP-Activated Protein Kinases"],"keywords":["Hypoxia (environmental)","Pulmonary artery","Cardiology","Smooth muscle","Internal medicine","Receptor","Chemistry","Medicine","Cell biology","Biology","Oxygen"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Affordable and clean energy"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-08T11:50:13.279216Z","pmid":null,"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":[]}