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

The extracellular pH, sodium and divalent cation concentrations influence the ATP-induced changes in cytosolic Ca2+ concentration ([Ca2+]i). This elevation of [Ca2+]i and activation of Ca2+-dependent Cl− channels represent a possible therapeutic approach in cystic fibrosis (CF). We investigated the changes of [Ca2+]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 Ca2+ signals independent of wild-type or mutant CFTR expression. The ATP-induced Ca2+ entry was either inhibited or stimulated by Zn2+ depending on the extracellular Na+ concentration. In Na+-free environment, Zn2+ and other divalent cations elicited a biphasic Ca2+ signal. Immunohistochemical data suggest that, multiple subtypes of P2XRs are expressed in these airway epithelial cells. In conclusion, Ca2+ entry is finely regulated by external ionic environment. Therefore, we speculate that properly compiled aerosols could influence efficacy of zinc-based therapy in CF.