{"doi":"10.1073/pnas.0902661107","title":"Mouse cystic fibrosis transmembrane conductance regulator forms cAMP-PKA–regulated apical chloride channels in cortical collecting duct","abstract":"<jats:p>\n                    The cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in many segments of the mammalian nephron, where it may interact with and modulate the activity of a variety of apical membrane proteins, including the renal outer medullary potassium (ROMK) K\n                    <jats:sup>+</jats:sup>\n                    channel. However, the expression of CFTR in apical cell membranes or its function as a Cl\n                    <jats:sup>−</jats:sup>\n                    channel in native renal epithelia has not been demonstrated. Here, we establish that CFTR forms protein kinase A (PKA)-activated Cl\n                    <jats:sup>−</jats:sup>\n                    channels in the apical membrane of principal cells from the cortical collecting duct obtained from mice. These Cl\n                    <jats:sup>−</jats:sup>\n                    channels were observed in cell-attached apical patches of principal cells after stimulation by forskolin/3-isobutyl-1-methylxanthine. Quiescent Cl\n                    <jats:sup>−</jats:sup>\n                    channels were present in patches excised from untreated tubules because they could be activated after exposure to Mg-ATP and the catalytic subunit of PKA. The single-channel conductance, kinetics, and anion selectivity of these Cl\n                    <jats:sup>−</jats:sup>\n                    channels were the same as those of recombinant mouse CFTR channels expressed in\n                    <jats:italic>Xenopus laevis</jats:italic>\n                    oocytes. The CFTR-specific closed-channel blocker CFTR\n                    <jats:sub>inh</jats:sub>\n                    -172 abolished apical Cl\n                    <jats:sup>−</jats:sup>\n                    channel activity in excised patches. Moreover, apical Cl\n                    <jats:sup>−</jats:sup>\n                    channel activity was completely absent in principal cells from transgenic mice expressing the ΔF508 CFTR mutation but was present and unaltered in ROMK-null mice. We discuss the physiologic implications of open CFTR Cl\n                    <jats:sup>−</jats:sup>\n                    channels on salt handling by the collecting duct and on the functional CFTR–ROMK interactions in modulating the metabolic ATP-sensing of ROMK.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2010,"id":631081,"datarank":0.5289540786924243,"base_score":3.5263605246161616,"endowment":3.5263605246161616,"self_citation_contribution":0.5289540786924243,"citation_network_contribution":0.0,"self_endowment_contribution":0.5289540786924243,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":33,"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":815434,"name":"Ke Dong","orcid":"0000-0002-1943-017X","position":1,"is_corresponding":false},{"id":225257,"name":"Marie E. Egan","orcid":"0000-0002-0567-6048","position":2,"is_corresponding":false},{"id":1635298,"name":"Gerhard H. Giebisch","orcid":null,"position":3,"is_corresponding":false},{"id":1635299,"name":"Emile L. Boulpaep","orcid":null,"position":4,"is_corresponding":false},{"id":1635300,"name":"Steven C. Hebert","orcid":null,"position":5,"is_corresponding":false},{"id":1143800,"name":"Ming Lu","orcid":"0000-0003-2763-2561","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Mouse cystic fibrosis transmembrane conductance regulator forms cAMP-PKA–regulated apical chloride channels in cortical collecting duct","abstract":"<jats:p>\n                    The cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in many segments of the mammalian nephron, where it may interact with and modulate the activity of a variety of apical membrane proteins, including the renal outer medullary potassium (ROMK) K\n                    <jats:sup>+</jats:sup>\n                    channel. However, the expression of CFTR in apical cell membranes or its function as a Cl\n                    <jats:sup>−</jats:sup>\n                    channel in native renal epithelia has not been demonstrated. Here, we establish that CFTR forms protein kinase A (PKA)-activated Cl\n                    <jats:sup>−</jats:sup>\n                    channels in the apical membrane of principal cells from the cortical collecting duct obtained from mice. These Cl\n                    <jats:sup>−</jats:sup>\n                    channels were observed in cell-attached apical patches of principal cells after stimulation by forskolin/3-isobutyl-1-methylxanthine. Quiescent Cl\n                    <jats:sup>−</jats:sup>\n                    channels were present in patches excised from untreated tubules because they could be activated after exposure to Mg-ATP and the catalytic subunit of PKA. The single-channel conductance, kinetics, and anion selectivity of these Cl\n                    <jats:sup>−</jats:sup>\n                    channels were the same as those of recombinant mouse CFTR channels expressed in\n                    <jats:italic>Xenopus laevis</jats:italic>\n                    oocytes. The CFTR-specific closed-channel blocker CFTR\n                    <jats:sub>inh</jats:sub>\n                    -172 abolished apical Cl\n                    <jats:sup>−</jats:sup>\n                    channel activity in excised patches. Moreover, apical Cl\n                    <jats:sup>−</jats:sup>\n                    channel activity was completely absent in principal cells from transgenic mice expressing the ΔF508 CFTR mutation but was present and unaltered in ROMK-null mice. We discuss the physiologic implications of open CFTR Cl\n                    <jats:sup>−</jats:sup>\n                    channels on salt handling by the collecting duct and on the functional CFTR–ROMK interactions in modulating the metabolic ATP-sensing of ROMK.\n                  </jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19767382","pmcid":null,"openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://www.pnas.org/content/pnas/107/13/6082.full.pdf","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.0902661107","host_type":"publisher"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2851921","host_type":"repository"}],"fields_of_study":[],"mesh_terms":[],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T22:47:34.427884Z","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":[]}