{"doi":"10.17615/n8z0-gh70","title":"Permeabilization via the P2X 7 Purinoreceptor Reveals the Presence of a Ca 2+ -activated Cl − Conductance in the Apical Membrane of Murine Tracheal Epithelial Cells","abstract":"Calcium-activated Cl(-) secretion is an important modulator of regulated ion transport in murine airway epithelium and is mediated by an unidentified Ca(2+)-stimulated Cl(-) channel. We have transfected immortalized murine tracheal epithelial cells with the cDNA encoding the permeabilizing P2X(7) purinoreceptor (P2X(7)-R) to selectively permeabilize the basolateral membrane and thereby isolate the apical membrane Ca(2+)-activated Cl(-) current. In P2X(7)-R-permeabilized cells, we have demonstrated that UTP stimulates a Cl(-) current across the apical membrane of CF and normal murine tracheal epithelial cells. The magnitude of the UTP-stimulated current was significantly greater in CF than in normal cells. Ion substitution studies demonstrated that the current exhibited a permselectivity sequence of Cl(-) > I(-) > Br(-) > gluconate(-). We have also determined a rank order of potency for putative Cl(-) channel blockers: niflumic acid > or = 5-nitro-2-(3-phenylpropylamino)benzoic acid > 4, 4'-diisothiocyanostilbene-2,2'-disulfonate > glybenclamide >> diphenlyamine-2-carboxylate, tamoxifen, and p-tetra-sulfonato-tetra-methoxy-calix[4]arene. Complete characterization of this current and the corresponding single channel properties could lead to the development of a new therapy to correct the defective airway surface liquid in cystic fibrosis patients.","journal":"UNC Libraries","year":2021,"id":231053,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":838231,"name":"E. S. Martsen","orcid":null,"position":1,"is_corresponding":false},{"id":523368,"name":"Sherif E. Gabriel","orcid":null,"position":2,"is_corresponding":false},{"id":838232,"name":"Mariya Makhlina","orcid":null,"position":3,"is_corresponding":false},{"id":105530,"name":"Richard C. Boucher","orcid":"0000-0002-5745-3989","position":4,"is_corresponding":false},{"id":838233,"name":"Mike I. Lethem","orcid":null,"position":5,"is_corresponding":false},{"id":402415,"name":"Emma Thomas","orcid":"0000-0001-8415-0521","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:55:12.400773Z","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":[]}