Evidence for a major route for zinc uptake in human red blood cells: [Zn(HCO3)2Cl]- influx through the [Cl-/HCO3-] anion exchanger.
The initial rate of Zn2+ uptake in human red cells was measured by atomic absorption. A very important fraction of Zn2+ uptake was inhibited by DIDS with IC50 = 0.3 microM (and by furosemide and bumetanide with IC50 of 200 and 500 microM, respectively). DIDS-sensitive Zn2+ uptake exhibited the following properties: 1) It required the simultaneous presence of both external HCO3- and Cl-. 2) In Cl- containing media, it was strongly stimulated by external HCO3- following a sigmoidal (S-shaped) and saturable function, which was fitted by a Hanes equation, with n = 2 and an apparent dissociation constant (for external HCO3-) of 5.3 +/- 0.9 mM (mean +/- SD of four experiments). The maximal rate of Zn2+ uptake at saturating HCO3- concentrations was 50.7 +/- 4.8 mmol (liter cells x h)-1. 3) In HCO3- containing media, it was strongly stimulated by external Cl- following a Michaelis-like equation with an apparent dissociation constant (for external Cl-) of 88 +/- 11 mM (mean +/- SD of three experiments). 4) Bicarbonate-stimulated Zn2+ uptake was inhibited by physiological concentrations of phosphate (sulfate was a much less potent inhibitor than phosphate). A kinetic analysis of the data strongly suggested that zinc was transported by the anion carrier in the form of the monovalent anion complex: [Zn(HCO3)2Cl]-.
Torrubia
J O
JO
INSERM U7/CNRS UA 318, Hôpital Necker, Paris, France.
Garay
R
R
D001639:Bicarbonates / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D008433:Mathematics; D010710:Phosphates / Q000494:pharmacology; D013431:Sulfates / Q000494:pharmacology; D015032:Zinc / Q000097:blood / Q000493:pharmacokinetics*
D001639:Bicarbonates; D002352:Carrier Proteins; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D010710:Phosphates; D013431:Sulfates; D015032:Zinc