title: Calcium entry is regulated by Zn2+ in relation to extracellular ionic environment in human airway epithelial cells.
abstract: The extracellular pH, sodium and divalent cation concentrations influence the ATP-induced changes in cytosolic Ca(2+) concentration ([Ca(2+)](i)). This elevation of [Ca(2+)](i) and activation of Ca(2+)-dependent Cl(-) channels represent a possible therapeutic approach in cystic fibrosis (CF). We investigated the changes of [Ca(2+)](i) in different external ionic environment, and P2X purinergic receptors (P2XRs) expression in the control and CF airway epithelial cells. The parallel removal of Na(+) and alkalinization of the extracellular solution increased the amplitude of sustained ATP-induced Ca(2+) signals independent of wild-type or mutant CFTR expression. The ATP-induced Ca(2+) entry was either inhibited or stimulated by Zn(2+) depending on the extracellular Na(+) concentration. In Na(+)-free environment, Zn(2+) and other divalent cations elicited a biphasic Ca(2+) signal. Immunohistochemical data suggest that, multiple subtypes of P2XRs are expressed in these airway epithelial cells. In conclusion, Ca(2+) entry is finely regulated by external ionic environment. Therefore, we speculate that properly compiled aerosols could influence efficacy of zinc-based therapy in CF.
authors.affiliation: Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary. hargitaidori@gmail.com
authors.forename: Dóra
authors.initials: D
authors.lastname: Hargitai
authors.forename: Agnes
authors.initials: A
authors.lastname: Pataki
authors.forename: Gábor
authors.initials: G
authors.lastname: Raffai
authors.forename: Márta
authors.initials: M
authors.lastname: Füzi
authors.forename: Tamás
authors.initials: T
authors.lastname: Dankó
authors.forename: László
authors.initials: L
authors.lastname: Csernoch
authors.forename: Péter
authors.initials: P
authors.lastname: Várnai
authors.forename: Gyula Péter
authors.initials: GP
authors.lastname: Szigeti
authors.forename: Akos
authors.initials: A
authors.lastname: Zsembery
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D001081:Apyrase / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002461:Cell Line, Transformed; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D004963:Estrenes / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects* / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000187:drug effects; D006593:Hexokinase / Q000494:pharmacology; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism; D058469:Receptors, Purinergic P2X; D012717:Sesquiterpenes / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D014162:Transfection / Q000379:methods; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D004963:Estrenes; D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D011760:Pyrrolidinones; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D012717:Sesquiterpenes; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D013498:Suramin; C046319:thapsigargicin; D000255:Adenosine Triphosphate; D012964:Sodium; D006593:Hexokinase; D001081:Apyrase; D015032:Zinc; D002118:Calcium