{"doi":"10.1074/jbc.275.23.17517","title":"Receptor-mediated Regulation of the Nonselective Cation Channels TRPC4 and TRPC5","abstract":null,"journal":"Journal of Biological Chemistry","year":2000,"id":608049,"datarank":0.9088684793372697,"base_score":6.059123195581797,"endowment":6.059123195581797,"self_citation_contribution":0.9088684793372697,"citation_network_contribution":0.0,"self_endowment_contribution":0.9088684793372697,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":427,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1561505,"name":"Timothy D. Plant","orcid":null,"position":1,"is_corresponding":false},{"id":152547,"name":"Alexander G. Obukhov","orcid":"0000-0002-3862-6004","position":2,"is_corresponding":false},{"id":518974,"name":"Thomas Hofmann","orcid":"0000-0003-4057-7165","position":3,"is_corresponding":false},{"id":666319,"name":"Thomas Gudermann","orcid":"0000-0002-0323-7965","position":4,"is_corresponding":false},{"id":153138,"name":"Günter Schultz","orcid":null,"position":5,"is_corresponding":false},{"id":521218,"name":"Michael Schaefer","orcid":"0000-0001-6255-3362","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Receptor-mediated Regulation of the Nonselective Cation Channels TRPC4 and TRPC5","abstract":"Mammalian transient receptor potential channels (TRPCs) form a family of Ca(2+)-permeable cation channels currently consisting of seven members, TRPC1-TRPC7. These channels have been proposed to be molecular correlates for capacitative Ca(2+) entry channels. There are only a few studies on the regulation and properties of the subfamily consisting of TRPC4 and TRPC5, and there are contradictory reports concerning the possible role of intracellular Ca(2+) store depletion in channel activation. We therefore investigated the regulatory and biophysical properties of murine TRPC4 and TRPC5 (mTRPC4/5) heterologously expressed in human embryonic kidney cells. Activation of G(q/11)-coupled receptors or receptor tyrosine kinases induced Mn(2+) entry in fura-2-loaded mTRPC4/5-expressing cells. Accordingly, in whole-cell recordings, stimulation of G(q/11)-coupled receptors evoked large, nonselective cation currents, an effect mimicked by infusion of guanosine 5'-3-O-(thio)triphosphate (GTPgammaS). However, depletion of intracellular Ca(2+) stores failed to activate mTRPC4/5. In inside-out patches, single channels with conductances of 42 and 66 picosiemens at -60 mV for mTRPC4 and mTRPC5, respectively, were stimulated by GTPgammaS in a membrane-confined manner. Thus, mTRPC4 and mTRPC5 form nonselective cation channels that integrate signaling pathways from G-protein-coupled receptors and receptor tyrosine kinases independently of store depletion. Furthermore, the biophysical properties of mTRPC4/5 are inconsistent with those of I(CRAC), the most extensively characterized store-operated current.","is_dataset_classified":null,"base_score":6.059123195581797,"endowment":6.059123195581797,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10837492","pmcid":null,"openalex_id":"https://openalex.org/W2162970979","authors":[],"funders":[],"total_grants":0,"fwci":11.7861,"citation_percentile":0.99324324,"influential_citations":0,"citation_trend":[{"year":2012,"count":15},{"year":2013,"count":13},{"year":2014,"count":21},{"year":2015,"count":14},{"year":2016,"count":11},{"year":2017,"count":13},{"year":2018,"count":12},{"year":2019,"count":14},{"year":2020,"count":14},{"year":2021,"count":13},{"year":2022,"count":6},{"year":2023,"count":7},{"year":2024,"count":15},{"year":2025,"count":6},{"year":2026,"count":8}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"http://www.jbc.org/article/S0021925819832726/pdf","host_type":"journal"},{"url":"http://www.jbc.org/article/S0021925819832726/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925819832726?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0021925819832726?httpAccept=text/plain","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1074/jbc.275.23.17517","host_type":"publisher"},{"url":"https://doi.org/10.1074/jbc.275.23.17517","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10837492","host_type":"repository"}],"fields_of_study":["Ion Channels and Receptors","Ion channel regulation and function","Neurobiology and Insect Physiology Research","Animals","Brain","Calcium Channels","Calcium Signaling","Cation Transport Proteins","Cell Line","Estrenes","GTP-Binding Protein alpha Subunits, Gq-G11","GTP-Binding Proteins","Guanosine 5'-O-(3-Thiotriphosphate)","Humans","Ion Channels","Kidney","Manganese","Mice","Phosphodiesterase Inhibitors","Pyrrolidinones","Receptor Protein-Tyrosine Kinases","Receptors, Cell Surface","Recombinant Proteins","TRPC Cation Channels","Thapsigargin","Transfection"],"mesh_terms":["Animals","Brain","Cell Line","Estrenes","Humans","Ion Channels","Kidney","Manganese","Phosphodiesterase Inhibitors","Pyrrolidinones","Receptors, Cell Surface","Recombinant Proteins","Transfection","Calcium Channels","Guanosine 5'-O-(3-Thiotriphosphate)","GTP-Binding Proteins","Thapsigargin","Calcium Signaling","Receptor Protein-Tyrosine Kinases","Cation Transport Proteins","GTP-Binding Protein alpha Subunits, Gq-G11","TRPC Cation Channels","Mice"],"keywords":["TRPC5","TRPC","Transient receptor potential channel","TRPC1","Cell biology","Chemistry","Receptor","TRPC3","TRPC6","G protein","Intracellular","Biophysics","Biochemistry","Biology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T07:25:56.632209Z","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":[]}