Calcium entry is regulated by Zn2+ in relation to extracellular ionic environment in human airway epithelial cells.

Dóra Hargitai, Agnes Pataki, Gábor Raffai, Márta Füzi, Tamás Dankó, László Csernoch, Péter Várnai, Gyula Péter Szigeti, Akos Zsembery

Journal: Respiratory physiology & neurobiology 2010;170(1):67-75

PMID: 19995619

Full Text on Elsevier Science View on PubMed

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.

Address: Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary. [email protected]

DOI: 10.1016/j.resp.2009.12.001

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MeSH Terms: Adenosine Triphosphate, Apyrase, Calcium, Calcium Signaling, Cell Line, Transformed, Cystic Fibrosis Transmembrane Conductance Regulator, Epithelial Cells, Estrenes, Extracellular Fluid, Gene Deletion, Gene Expression Regulation, Hexokinase, Humans, Lactones, Platelet Aggregation Inhibitors, Pyrrolidinones, Receptors, Purinergic P2, Receptors, Purinergic P2X, Sesquiterpenes, Sodium, Suramin, Transfection, Zinc