Location of the chloride self-inhibitory site of the human erythrocyte anion exchange system.
Experiments were performed with intact human red blood cells to determine whether the inhibitory effects of high Cl- concentrations on Cl- exchange are primarily due to interaction at the cytoplasmic or the external surface of the membrane. When internal Cl- was varied from 150 mM to 600 mM Cl- (using the nystatin technique), keeping external Cl- constant at 150 mM (with sucrose added to maintain osmotic balance), Cl- exchange was inhibited almost exactly as much as when both internal and external Cl- were increased from 150 mM to 600 mM. On the other hand, if internal Cl- was maintained constant at 600 mM, variation of external Cl- (with either sucrose, gluconate, or citrate-sucrose mixtures replacing Cl-) had no consistent effect on Cl- exchange. Even if internal Cl- was kept at 150 mM by substitution of gluconate for Cl-, an increase in external Cl- from 150 mM to 600 mM did not significantly inhibit Cl- exchange. Thus the self-inhibitory effects of Cl- seem to be caused primarily by binding to a site at the cytoplasmic side of the membrane. External Br-, on the other hand, did cause a significant inhibition of Cl- exchange. In contrast to the inhibitory effects of Cl- at neutral pH, at very high pH (around pH 11) there is an activation of Cl- exchange at very high Cl- concentrations. This effect, however, depends on binding of Cl- to an external site. Thus there seem to be at least two different low-affinity Cl- binding sites, one at the cytoplasmic side, which inhibits Cl- exchange, and one at the external side, which activates Cl- exchange at high external pH.
D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D001665:Binding Sites; D001693:Biological Transport, Active; D001966:Bromine / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D002712:Chlorides / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D005942:Gluconates / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007474:Ion Exchange; D009761:Nystatin / Q000494:pharmacology
D001457:Anion Exchange Protein 1, Erythrocyte; D002712:Chlorides; D005942:Gluconates; D007473:Ion Channels; D009761:Nystatin; C030691:gluconic acid; D001966:Bromine