Theoretical and experimental discrimination between Cl(-)-H+ symporters and Cl-/OH- antiporters

Abstract

A Cl(-)-H+ symport and a Cl-/OH- antiport cannot be readily distinguished physicochemically, but a kinetic distinction is theoretically possible, because a Cl(-)-H+ symporter involves a two-site carrier whereas a Cl-/OH- antiporter involves a single-site carrier. Accordingly, we have developed kinetic models and equations that we have tested by studying Cl- uptake by isolated guinea pig ileal brush-border membrane vesicles as a function of Cl- or H+ concentration. We conclude that a two-site Cl(-)-H+ symporter with a 1:1 stoichiometry explains the pH-dependent Cl- uptake and Cl-/Cl- exchange activities of the brush-border membrane in terms of a single random nonobligatory mobile carrier where exchange occurs by counterflow. This symport, probably involving an anion exchanger (AE 2) protein, differs, therefore, functionally from the erythrocyte's band 3 AE1, which involves an antiport. The question is whether members of the AE gene family can be functionally diverse, even when their primary structures exhibit up to 50% overall homologies.