Aims: 

An increase of cytosolic Ca²⁺ concentrations ([Ca²⁺]_i) can stimulate Ca²⁺-activated Cl^- channels (CaCC) that represent therapeutic targets in cystic fibrosis (CF). We have previously demonstrated that zinc and ATP induced a sustained, reversible, and reproducible increase in [Ca²⁺]_i in both control and CF airway epithelial cells. We could also demonstrate that this cytosolic calcium signal promoted sustained Cl^- secretion of nasal epithelia in CF mice. Here we aimed to investigate the effects of external zinc on Ca²⁺ entry and Cl^- secretory pathways, separately.

Methods: 

Single cell Ca²⁺ measurements were performed using Fluo-3/AM fluorescent dye in CF airway epithelial cells. Ion currents were detected in whole cell configuration of the patch clamp technique.

Results: 

In the presence of extracellular Na⁺ the ATP-induced Ca²⁺ entry was inhibited by Zn²⁺. In Na⁺-free environment Zn²⁺ elicited a sustained Ca²⁺ signal in pH_o-dependent manner both in the presence and absence of ATP. Ca²⁺ entry promoted by extracellular alkalinization stimulated CaCC activity which was significantly reduced by Zn²⁺.

Conclusions: 

Ca²⁺ entry from the extracellular space is finely regulated by external ionic environment. Extracellular Zn²⁺ directly blocked, however indirectly enhanced the activity of Cl^- conductance.