SLC26 Cl-/HCO3- exchangers in the kidney: roles in health and disease

Solute-linked carrier 26 (SLC26) isoforms constitute a conserved family of anion transporters with 10 distinct members. Except for SLC26A5 (prestin), all can operate as multifunctional anion exchangers, with three members (SLC26A7, SLC26A9, and SLC26A11) also capable of functioning as chloride channels. Several SLC26 isoforms can specifically mediate Cl-/HCO3- exchange. These include SLC26A3, A4, A6, A7, A9, and A11, which are expressed in the kidney except for SLC26A3 (DRA), which is predominantly expressed in the intestine. SLC26 Cl-/HCO3- exchanger isoforms display unique nephron segment distribution patterns with distinct subcellular localization in the kidney tubules. Together with studies in pathophysiologic states and the examination of genetically engineered mouse models, the evolving picture points to important roles for the SLC26 family in health and disease states. This review summarizes recent advances in the characterization of the SLC26 Cl-/HCO3- exchangers in the kidney with emphasis on their essential role in diverse physiological processes, including chloride homeostasis, oxalate excretion and kidney stone formation, vascular volume and blood pressure regulation, and acid–base balance.