Cation-dependent uptake of zinc in human fibroblasts.
The influence of K+ and Ca2+ on Zn2+ transport into cultured human fibroblasts was investigated. Zn2+ uptake was markedly reduced in the presence of both valinomycin and nigericin (electrogenic and electroneutral K+ ionophores, respectively), and by reduction in the transmembrane K+ gradient produced by replacement of extracellular K+ with Na+, suggesting that Zn2+ may be driven by a Zn2+/K+ counter-transport system. To test the counter-transport hypothesis, we used 86Rb as an analog of K+ for efflux studies. The rate of Rb+ efflux was 3760 times that of Zn2+ uptake, thus the component of K+ involved in the Zn2+ counter-transport system was only a small proportion of the total K+ efflux. In investigating the effect of Ca2+ on Zn2+ uptake, we identified two components: (1) a basal Zn2+ uptake pathway, independent of hormonal or growth factors which does not require extracellular Ca2+ and (2) a Ca(2+)-dependent mechanism. The absence of Ca2+ decreased Zn2+ uptake, while increasing extracellular Ca2+ stimulated Zn2+ uptake. The effect was mediated by Ca2+ influx as the ionophores A23187 and ionomycin also stimulated Zn2+ uptake. We could not ascribe the Ca2+ effect to known Ca2+ influx pathways. We conclude that Zn2+ uptake occurs by a K(+)-dependent process, possibly by Zn2+/K+ counter-transport and that a component of this is also Ca(2+)-dependent.
Ackland
M L
ML
Department of Biological and Chemical Sciences, Deakin University, Victoria, Australia.
McArdle
H J
HJ
D017920:Antiporters / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007476:Ionophores / Q000494:pharmacology*; D009550:Nigericin / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D012413:Rubidium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D014634:Valinomycin / Q000494:pharmacology; D015032:Zinc / Q000493:pharmacokinetics*
D017920:Antiporters; D007476:Ionophores; D014634:Valinomycin; D012964:Sodium; D015032:Zinc; D012413:Rubidium; D009550:Nigericin; D011188:Potassium; D002118:Calcium