Physiological consequences of oxygen-dependent chloride binding to hemoglobin

The Po₂-dependent binding of chloride to Hb decreases the Cl^- concentration of the red blood cell (RBC) intracellular fluid in venous blood to ∼1-3 mmol/l less than that in arterial blood. This change is physiologically important because 1) Cl^- is a negative heterotropic allosteric effector of Hb that competes for binding sites with 2,3-bisphosphoglycerate and CO₂ and decreases oxyhemoglobin affinity in several species; 2) it may help reconcile several longstanding problems with measured values of the Donnan ratios for Cl^-, HCO₃^-, and H⁺ across the RBC membrane that are used to calculate total CO₂ carriage, ion flux rates, and membrane potentials; 3) it is a factor in the change in the dissociation constant for the combined nonvolatile weak acids of Hb associated with the Haldane effect; and 4) it diminishes the decrease in strong ion difference in the RBC intracellular fluid that would otherwise occur from the chloride shift and prevent the known increase of HCO₃^- concentration in that compartment.