Zinc inhibition of potassium efflux in depolarized frog muscle and its modification by external hydrogen ions and diethylpyrocarbonate treatment.
Efflux of 42K+ was measured in frog sartorius muscles equilibrated in hyperosmotic depolarizing solutions. At the internal potentials obtained, K+ passes mainly through the inward rectifier potassium channels. Inhibition of K+ efflux by external Zn2+ (0.25 to 15 mM) differs in three significant ways from inhibition by Ba2+. (1) The dose-response relation does not correspond to action at a single site. (2) The Zn2+-sensitivity of K+ efflux does not depend on [K+]0 at constant internal potential. (3) Zn2+ inhibition is reduced by hydrogen ions, while Ba2+ inhibition is unaffected. Further, the Ba2+-sensitivity of K+ efflux is not altered by a half-inhibiting Zn2+ concentration, suggesting that the two ions do not interact at a common site. The histidine-modifying reagent diethylpyrocarbonate (DEPC) reduces Zn2+ inhibition. After DEPC treatment Zn2+ inhibition is further reduced by low pH. DEPC has little effect on Ba2+ inhibition. Zn2+ inhibition is not altered by treatment with the sulfhydryl reagents 5,5'-dithio-bis(2-nitrobenzoic acid) or dithiothreitol. The results can be described by either of two models in which two sites can bind Zn2+ and one or both of the sites may also bind H+. When both sites bind Zn2+, K+ efflux is inhibited, and a third site may then bind H+. The effects of DEPC can be accounted for by a decrease in H+ affinity of the first two sites by a factor of 50, and a decrease in Zn2+ affinity of these sites and of the H+ affinity of the third site by about one order of magnitude.
D000818:Animals; D001464:Barium / Q000494:pharmacology; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology*; D005561:Formates / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008433:Mathematics; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D009132:Muscles / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D011522:Protons; D011894:Rana pipiens; D015032:Zinc / Q000494:pharmacology*
D005561:Formates; D011522:Protons; D001464:Barium; D015032:Zinc; D004047:Diethyl Pyrocarbonate; D011188:Potassium