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

Lookup NU author(s): Dr Georgina Carr, Jamie Wright, Professor Nicholas Simmons


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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 Omega A cm(2) to 1,551 +/- 225.6 Omega A cm(2); 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 Omega A cm(2)). 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 Ca-45 fluxes increased approximately twofold when driven by a basal positive Na:NMDG bi-ionic p.d., but with basal 10 mM ZnCl2, Ca-45 fluxes decreased approximately twofold. Neither ZO-1 nor occludin distribution was altered after similar to 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.

Publication metadata

Author(s): Carr G, Wright JA, Simmons NL

Publication type: Article

Publication status: Published

Journal: Journal of Membrane Biology

Year: 2010

Volume: 237

Issue: 2-3

Pages: 115-123

Print publication date: 06/11/2010

ISSN (print): 0022-2631

ISSN (electronic): 1432-1424

Publisher: Springer New York LLC


DOI: 10.1007/s00232-010-9312-z


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