Mechanisms of dietary Cu uptake in freshwater rainbow trout: Evidence for Na-assisted Cu transport and a specific metal carrier in the intestine

Copper (Cu) is both a vital nutrient and a potent toxicant. The objective of this study was to analyze the mechanistic nature of intestinal Cu transport in rainbow trout using radiolabeled Cu (⁶⁴Cu) and an in vitro gut sac technique. Reduction of mucosal NaCl levels inhibited Cu transport while increase caused stimulation; Na₂SO₄ had an identical effect, implicating Na⁺ rather than the anion. These responses were unrelated to solvent drag, osmotic pressure or changes in transepithelial potential. The presence of elevated luminal Ag stimulated Cu and Na⁺ uptake. Phenamil caused a partial inhibition of both Cu and Na⁺ uptake while hypercapnia stimulated Na⁺ and Cu transport. Cu uptake was sensitive to luminal pH and inhibited by a tenfold excess of Fe and Zn. These factors had no effect on Na⁺ uptake. On the basis of these results we propose a novel Na⁺-assisted mechanism of Cu uptake wherein the Na⁺ gradient stimulates an increase in the H⁺ concentration of the brushborder creating a suitable microenvironment for the effective transport of Cu via either DMT1 or Ctr1.