Molecular physiology of the renal chloride-formate exchanger.

Renal apical chloride-base exchangers are essential to electrolyte and acid-base homeostasis. Different functional isoforms of apical anion exchangers have been identified in kidney proximal tubule and cortical collecting duct. Included amongst these are the following: chloride-formate, chloride-oxalate, and chloride-hydroxyl exchangers in proximal tubule; and chloride-bicarbonate exchanger in cortical collecting duct. Chloride-formate exchange, which was first identified in kidney proximal tubule, works in parallel with the apical sodium-hydrogen exchanger, and is thought to reabsorb the bulk of luminal chloride. Despite numerous studies, the molecular identities of apical chloride-base exchangers have remained unknown. Recent studies have identified a new class of anion exchangers, including pendrin (encoded by the PDS gene) and downregulated in adenoma (DRA, encoded by the DRA gene). Pendrin is expressed in the kidney, whereas DRA is not. Functional studies indicate that pendrin can function in chloride-formate and chloride-base exchange modes. It is unlikely that pendrin is the apical chloride-formate exchanger in the kidney proximal tubule. However, it is the only molecule that has been shown to mediate chloride-formate exchange. In the present review, recent studies regarding the renal distribution and membrane localization of pendrin, and its functional properties, including its roles in chloride reabsorption and base excretion, are addressed.