{"doi":"10.3390/ijms24043259","title":"The Molecular Heterogeneity of Store-Operated Ca2+ Entry in Vascular Endothelial Cells: The Different roles of Orai1 and TRPC1/TRPC4 Channels in the Transition from Ca2+-Selective to Non-Selective Cation Currents","abstract":"<jats:p>Store-operated Ca2+ entry (SOCE) is activated in response to the inositol-1,4,5-trisphosphate (InsP3)-dependent depletion of the endoplasmic reticulum (ER) Ca2+ store and represents a ubiquitous mode of Ca2+ influx. In vascular endothelial cells, SOCE regulates a plethora of functions that maintain cardiovascular homeostasis, such as angiogenesis, vascular tone, vascular permeability, platelet aggregation, and monocyte adhesion. The molecular mechanisms responsible for SOCE activation in vascular endothelial cells have engendered a long-lasting controversy. Traditionally, it has been assumed that the endothelial SOCE is mediated by two distinct ion channel signalplexes, i.e., STIM1/Orai1 and STIM1/Transient Receptor Potential Canonical 1(TRPC1)/TRPC4. However, recent evidence has shown that Orai1 can assemble with TRPC1 and TRPC4 to form a non-selective cation channel with intermediate electrophysiological features. Herein, we aim at bringing order to the distinct mechanisms that mediate endothelial SOCE in the vascular tree from multiple species (e.g., human, mouse, rat, and bovine). We propose that three distinct currents can mediate SOCE in vascular endothelial cells: (1) the Ca2+-selective Ca2+-release activated Ca2+ current (ICRAC), which is mediated by STIM1 and Orai1; (2) the store-operated non-selective current (ISOC), which is mediated by STIM1, TRPC1, and TRPC4; and (3) the moderately Ca2+-selective, ICRAC-like current, which is mediated by STIM1, TRPC1, TRPC4, and Orai1.</jats:p>","journal":"International Journal of Molecular Sciences","year":2023,"id":29201,"datarank":0.9592736295857544,"base_score":3.58351893845611,"endowment":3.58351893845611,"self_citation_contribution":0.5375278407684165,"citation_network_contribution":0.4217457888173378,"self_endowment_contribution":0.5375278407684165,"citer_contribution":0.4217457888173378,"corpus_percentile":null,"corpus_rank":null,"citation_count":35,"citer_count":18,"citers_with_citation_signal":17,"citers_with_endowment":17,"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":161594,"name":"Valentina Brunetti","orcid":null,"position":1,"is_corresponding":false},{"id":161595,"name":"Angelica Perna","orcid":"0000-0002-7853-9159","position":2,"is_corresponding":false},{"id":161596,"name":"Germano Guerra","orcid":"0000-0002-4342-962X","position":3,"is_corresponding":false},{"id":161597,"name":"Teresa Soda","orcid":"0000-0002-7728-6815","position":4,"is_corresponding":false},{"id":161598,"name":"Roberto Berra-Romani","orcid":"0000-0003-4884-0925","position":5,"is_corresponding":false},{"id":161593,"name":"Francesco Moccia","orcid":"0000-0003-0010-0098","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36834672","pmcid":"PMC9967124","openalex_id":"https://openalex.org/W4319600833","authors":[],"funders":[{"funder_name":"Italian Ministry of Education, University and Research (MIUR)","grant_id":"828984 (LION-HEARTED)","title":null},{"funder_name":"Italian Ministry of Education, University and Research (MIUR)","grant_id":"CVU121216","title":null},{"funder_name":"University of Pavia","grant_id":"Fondo Ricerca Giovani","title":null},{"funder_name":"talian Ministry of Education, University and Research (MIUR)","grant_id":"Dipartimenti di Eccellenza Program (2018-2022) - Dept. of Biology and Biotechnology \"L. 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