AJP - Cell Physiology, Vol 259, Issue 4 C570-C576, Copyright © 1990 by American Physiological Society
Chloride (or bicarbonate)-dependent copper uptake through the anion exchanger in human red blood cells
J. O. Alda and R. Garay
Hopital Necker, Institut National de la Sante et de la Recherche Medicale, Paris, France.
The initial rate of Cu2+ uptake in human red blood cells was measured by
atomic absorption. About 80% of Cu2+ uptake was inhibited by
4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) concentrations
greater than 5-10 microM. DIDS-sensitive Cu2+ uptake required the presence
of external HCO3- or external Cl-. Cl- strongly stimulated Cu2+ uptake
following a Michaelis-like function, with apparent dissociation constant
(KCl) of 72 +/- 9.4 (SD) mM (n = 6 experiments). HCO3- stimulated
DIDS-sensitive Cu2+ uptake following a Michaelis-like function, with
apparent dissociation constant (Kbic) of 10 +/- 1.9 (SD) mM (n = 4
experiments). Maximal rates (of Cl(-)- or HCO3(-)-stimulated Cu2+ uptake)
were nonadditive. DIDS-sensitive Cu2+ uptake was not modified by
physiological concentrations of phosphate or sulfate. Conversely, it was
strongly inhibited by physiological concentrations of L-histidine and
cysteine (at a Cu2+ concentration of 100 microM, these physiological
ligands exhibited KHis and KCys of 50 and 80 microM, respectively). By
using a copper-selective electrode, we found that at pH 7-7.4 copper is
associated with OH-, particularly in the form of Cu(OH)2 complexes. In
conclusion, the anion exchanger is the major transport mechanism for red
blood cell Cu2+ uptake. The translocating species can be the monovalent
anion complexes of copper with OH-, Cl-, and/or HCO3-.
