Zinc blocks apical membrane anion exchange in gallbladder epithelium.
The effect of Zn2+ on Cl- transport across the apical membrane of Necturus gallbladder epithelium was studied with intracellular conventional and Cl(-)-selective microelectrodes and measurements of apparent base secretion. Most studies were done on tissues incubated in HEPES-buffered solutions; intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels were elevated by adding to the serosal bathing medium either theophylline or dibutyryl cAMP. Under these conditions, Zn2+ (added to mucosal solution) had no effect on membrane voltages, apparent cell membrane resistance ratio, or rapid depolarization induced by reducing mucosal solution [Cl-]. However, Zn2+ reduced the rate of cell membrane repolarization during exposure to the low-Cl- solution and decreased significantly the rate of fall of intracellular Cl- activity (alpha Cli) elicited by lowering mucosal solution [Cl-]. Both effects were time dependent, became significant after 10 min, and were slowly reversible. In tissues not stimulated by cAMP and incubated in a HCO3-CO2-buffered solution, Zn2+ also reduced the rate of fall of alpha Cli on lowering mucosal solution [Cl-]. Base secretion from cells to mucosal solution was assessed from changes in mucosal pH on stopping superfusion with a poorly buffered (1 mM HEPES) medium in the presence of 1 mM amiloride or a Na(+)-free medium, without cAMP stimulation. Exposure to Zn2+ reduced the alkalinization observed with both protocols. We conclude that Zn2+ has no effect on apical membrane Cl- conductance stimulated by cAMP and inhibits Cl(-)-HCO3- exchange. The slow onset and reversal of the effects suggests slow binding of Zn2+, a covalent modification of the exchanger, or an effect requiring Zn2+ transport to the cell interior.
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77550.
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D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000838:Anions; D003994:Bucladesine / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism / Q000502:physiology*; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005704:Gallbladder / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008565:Membrane Proteins / Q000502:physiology*; D009092:Mucous Membrane / Q000187:drug effects / Q000502:physiology; D009337:Necturus; D013806:Theophylline / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology*
D000838:Anions; D018118:Chloride Channels; D002712:Chlorides; D007473:Ion Channels; D008565:Membrane Proteins; D003994:Bucladesine; D000584:Amiloride; D013806:Theophylline; D015032:Zinc