Epithelial Barrier Resistance is Increased by the Divalent Cation Zinc in Cultured MDCKII Epithelial Monolayers

Topical zinc applications promote wound healing and epithelialization. "Leaky" MDCKII epithelia exposed to apical ZnCl? (10 mM) showed a time-dependent increase (t (0.5) 22.2 ± 2.7 min) of transepithelial resistance (R (t)) from 82.3 ± 2.4 Ω cm2 to 1,551 ± 225.6 Ω cm2; the increase was dose-dependent, being observed at 3 mM but not at 1 mM. Basal Zn2+ applications also increased epithelial resistance (at 10 mM to 323 ± 225.6 Ω cm2). The linear current-voltage relationship in control epithelia changed after apical 10 mM ZnCl? to show rectification. Voltage deflections resulting from inward currents showed time-dependent relaxation (basal potential difference (p.d.)-positive), with outward currents being time-independent. Cation selectivity was tested after apical ZnCl? elevated resistance; both the NaCl:mannitol (basal replacement) dilution p.d. and the choline:Na bi-ionic p.d. decreased (P(Na)/P(Cl) from 4.9 to 2.3 and P(Na)/P(choline) from 3.8 to 2.1, respectively). Transepithelial paracellular basal to apical ??Ca fluxes increased approximately twofold when driven by a basal positive Na:NMDG bi-ionic p.d., but with basal 10 mM ZnCl?, ??Ca fluxes decreased approximately twofold. Neither ZO-1 nor occludin distribution was altered after ~2-h exposure to apical 10 mM ZnCl?. However, claudin-2, though present at the tight junction, increased within the cell. Increased epithelial barrier resistance by Zn2+ is due to modification of the paracellular pathway, most probably by multiple mechanisms.