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 ZnCl₂ (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 ZnCl₂ 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 ZnCl₂ 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 ⁴⁵Ca fluxes increased approximately twofold when driven by a basal positive Na:NMDG bi-ionic p.d., but with basal 10 mM ZnCl₂, ⁴⁵Ca fluxes decreased approximately twofold. Neither ZO-1 nor occludin distribution was altered after ~2-h exposure to apical 10 mM ZnCl₂. 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.
Epithelial Research Group, ICAMB, Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE24HH, UK.
Georgina
G
Carr
Jamie A
JA
Wright
Nicholas L
NL
Simmons
D000818:Animals; D002460:Cell Line; D002712:Chlorides / Q000494:pharmacology; D004285:Dogs; D004594:Electrophysiology; D004847:Epithelial Cells / Q000187:drug effects*; D018613:Microscopy, Confocal; D019108:Tight Junctions / Q000187:drug effects; D015032:Zinc; D017967:Zinc Compounds / Q000494:pharmacology
D002712:Chlorides; D017967:Zinc Compounds; C016837:zinc chloride; D015032:Zinc