Novel functions of the anion exchanger AE4 (SLC4A9)

The kidney plays a crucial role in acid-base homeostasis. In the distal nephron, α-intercalated cells contribute to urinary acid (H⁺) secretion and β-intercalated cells accomplish urinary base (HCO₃^-) secretion. β-intercalated cells regulate the acid base status through modulation of the apical Cl^-/HCO₃^- exchanger pendrin (SLC26A4) activity. In this review, we summarize and discuss our current knowledge of the physiological role of the renal transporter AE4 (SLC4A9). The AE4, as cation-dependent Cl^-/HCO₃^- exchanger, is exclusively expressed in the basolateral membrane of β-intercalated cells and is essential for the sensing of metabolic acid-base disturbances in mice, but not for renal sodium reabsorption and plasma volume control. Potential intracellular signaling pathways are discussed that might link basolateral acid-base sensing through the AE4 to apical pendrin activity.