{"doi":"10.1038/sj.bjp.0702416","title":"Activation of three types of voltage‐independent Ca<sup>2+</sup> channel in A7r5 cells by endothelin‐1 as revealed by a novel Ca<sup>2+</sup> channel blocker LOE 908","abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>We have shown that in addition to voltage‐operated Ca<jats:sup>2+</jats:sup> channel (VOC), endothelin‐1 (ET‐1) activates two types of Ca<jats:sup>2+</jats:sup>‐permeable nonselective cation channel (NSCC) in A7r5 cells: its lower concentrations (1 n<jats:sc>M</jats:sc>; lower [ET‐1]) activate only an SK&amp;F 96365‐resistant channel (NSCC‐1), whereas its higher concentrations (10 n<jats:sc>M</jats:sc>; higher [ET‐1]) activate an SK&amp;F 96365‐sensitive channel (NSCC‐2) as well.</jats:p></jats:list-item>\n<jats:list-item><jats:p>We now characterized the effects of a blocker ofCa<jats:sup>2+</jats:sup> entry channel LOE 908 on NSCCs and store‐operatedCa<jats:sup>2+</jats:sup> channel (SOCC) in A7r5 cells, and using twodrugs, clarified the involvement of these channels in the ET‐1‐inducedincrease in the intracellular free Ca<jats:sup>2+</jats:sup> concentrations([Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>). Whole‐cell recordingsand [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> monitoring withfluo‐3 were used.</jats:p></jats:list-item>\n<jats:list-item><jats:p>LOE 908 up to 10 μ<jats:sc>M</jats:sc> had no effect on increases in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> induced by thapsigargin or ionomycin, but SK&amp;F 96365 abolished them.</jats:p></jats:list-item>\n<jats:list-item><jats:p>In the cells clamped at −60 mV, both lower and higher [ET‐1] induced inward currents with linear iv relationships and the reversal potentials of −15.0 mV. Thapsigargin induced no currents.</jats:p></jats:list-item>\n<jats:list-item><jats:p>In the presence of nifedipine, lower [ET‐1] induced a sustained increase in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>, whereas higher [ET‐1] induced a transient peak and a sustained increase. The sustained increases by lower and higher [ET‐1] were abolished by removal of extracellular Ca<jats:sup>2+</jats:sup>, and they were suppressed by LOE 908 to 0 and 35%, respectively, with the LOE 908‐resistant part being abolished by SK&amp;F 96365.</jats:p></jats:list-item>\n<jats:list-item><jats:p>These results show that LOE 908 is a blocker of NSCCs without effect on SOCC, and that the increase in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> at lower [ET‐1] results from Ca<jats:sup>2+</jats:sup> entry through NSCC‐1 in addition to VOC, whereas the increase at higher [ET‐1] involves NSCC‐1, NSCC‐2 and SOCC in addition to VOC.</jats:p></jats:list-item>\n</jats:list>\n</jats:p><jats:p><jats:italic>British Journal of Pharmacology</jats:italic> (1999) <jats:bold>126</jats:bold>, 1107–1114; doi:<jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038/sj.bjp.0702416\">10.1038/sj.bjp.0702416</jats:ext-link></jats:p>","journal":"British Journal of Pharmacology","year":1999,"id":24802,"datarank":3.198251552997741,"base_score":4.2626798770413155,"endowment":4.2626798770413155,"self_citation_contribution":0.6394019815561974,"citation_network_contribution":2.5588495714415433,"self_endowment_contribution":0.6394019815561974,"citer_contribution":2.5588495714415433,"corpus_percentile":null,"corpus_rank":null,"citation_count":70,"citer_count":48,"citers_with_citation_signal":42,"citers_with_endowment":42,"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":146650,"name":"Soichi Miwa","orcid":null,"position":1,"is_corresponding":false},{"id":147760,"name":"Xiao‐Feng Zhang","orcid":null,"position":2,"is_corresponding":false},{"id":147761,"name":"Tetsuya Minowa","orcid":null,"position":3,"is_corresponding":false},{"id":147762,"name":"Taijiro Enoki","orcid":null,"position":4,"is_corresponding":false},{"id":146649,"name":"Yasuo Okamoto","orcid":null,"position":5,"is_corresponding":false},{"id":147763,"name":"Hiroshi Hasegawa","orcid":null,"position":6,"is_corresponding":false},{"id":147764,"name":"Hidekatsu Furutani","orcid":null,"position":7,"is_corresponding":false},{"id":147766,"name":"Makoto Okazawa","orcid":null,"position":8,"is_corresponding":false},{"id":147768,"name":"Masatsune Ishikawa","orcid":null,"position":9,"is_corresponding":false},{"id":147770,"name":"Nobuo Hashimoto","orcid":null,"position":10,"is_corresponding":false},{"id":98023,"name":"Tomoh Masaki","orcid":null,"position":11,"is_corresponding":false},{"id":146647,"name":"Yasushi Iwamuro","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.2626798770413155,"endowment":4.2626798770413155,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10204997","pmcid":"PMC1565887","openalex_id":"https://openalex.org/W2122146739","authors":[],"funders":[],"total_grants":0,"fwci":3.6592,"citation_percentile":0.93707963,"influential_citations":2,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":1},{"year":2014,"count":1},{"year":2016,"count":1},{"year":2017,"count":1},{"year":2021,"count":1}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1038/sj.bjp.0702416","host_type":"journal"},{"url":"https://europepmc.org/articles/pmc1565887?pdf=render","host_type":"GREEN"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1038/sj.bjp.0702416","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1038%2Fsj.bjp.0702416","host_type":"publisher"},{"url":"https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1038/sj.bjp.0702416","host_type":"publisher"},{"url":"https://doi.org/10.1038/sj.bjp.0702416","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10204997","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1565887","host_type":"repository"}],"fields_of_study":["Ion channel regulation and function","Cardiac electrophysiology and arrhythmias","Neuroscience and Neuropharmacology Research","Chemistry","Medicine","Biology","Acetamides","Animals","Calcium","Calcium Channel Blockers","Calcium Channels","Cations","Cells, Cultured","Drug Interactions","Endothelin-1","Imidazoles","Ionomycin","Isoquinolines","Patch-Clamp Techniques","Rats","Thapsigargin"],"mesh_terms":["Acetamides","Animals","Calcium","Calcium Channel Blockers","Cations","Cells, Cultured","Drug Interactions","Imidazoles","Isoquinolines","Calcium Channels","Ionomycin","Patch-Clamp Techniques","Thapsigargin","Endothelin-1","Rats"],"keywords":["Thapsigargin","Channel blocker","Ionomycin","Nifedipine","Endothelin 1","Extracellular","Chemistry","Biophysics","Fura-2","Intracellular","Voltage-dependent calcium channel","Endocrinology","Internal medicine","Calcium","Biochemistry","Biology","Medicine","Cytosol","Receptor"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Clean water and sanitation"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T23:16:52.318615Z","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":[]}