Proposed working model of Cu absorption in the catfish intestine. Cu normally enters the cell through apical cation channels and leaves the cell basolaterally, either via vesicular Cu-ATPase activity or by Cu/anion symport. Intracellular [Cl−] is maintained slightly above equilibrium by apical Na+/Cl− and Na+/K+/2Cl− cotransport, and Cl− normally exits the cell through the voltagedependent basolateral Cl− channel, by K+/Cl− symport and by Cl−/HCO3− antiport. Blockade of these normal basolateral routes of Cl− efflux with DIDS causes intracellular concentrations of both K+ and Cl− to rise. In the presence of Cu, the Cl− is quickly eliminated from the cell to the blood via Cu/anion symport, and so no net change in tissue Cl− concentration is observed while Cu uptake to the blood increases. Cu itself or activation of Cu oxidases may block K+ channels, preventing K+ efflux so that tissue [K+] rises dramatically. The stoichiometry of the Cu/anion symport is uncertain, but the preferred anion is probably Cl−. Putative basolateral Cu/iron and Cu/zinc antiports are excluded from the diagram for clarity. −ve, negative.