The Anion Exchanger Pendrin (SLC26A4) and Renal Acid-base Homeostasis

Abstract

The anion exchanger pendrin (Pds, SLC26A4) transports various anions including bicarbonate, chloride and iodide. In the kidney, pendrin is exclusively expressed on the luminal pole of bicarbonate-secretory type B intercalated cells. Genetic ablation of pendrin in mice abolishes luminal chloride-bicarbonate exchanger activity from type B intercalated cells suggesting that pendrin is the apical bicarbonate extruding pathway. The renal expression of pendrin is developmentally adapted and pendrin positive cells originate from both the uretric bud and mesenchyme. In adult kidney, pendrin expression and activity is regulated by systemic acid-base status, dietary electrolyte intake (mostly chloride), and hormones such as angiotensin II and aldosterone which can affect subcellular localization, the relative number of pendrin expressing cells, and the overall abundance consistent with a role of pendrin in maintaining normal acid-base homeostasis. This review summarizes recent findings on the role and regulation of pendrin in the context of the kidneys role in acid-base homeostasis in health and disease.

α-Ketoglutarate regulates acid-base balance through an intrarenal paracrine mechanism

“…This specific cellular localization was validated by the absence of costaining with parvalbumin (a marker of the early distal convoluted tubule; Supplemental Figure 1, C-E), the sodium chloride cotransporter (NCC) (a marker of the early and late distal convoluted tubule; Supplemental Figure 1, F-H), the β subunit of the amiloride-sensitive epithelial sodium channel (ENaC) (a marker of the late distal convoluted tubule and the principal cells of the CNT and the CCD; Supplemental Figure 1 The type B and non-A-non-B intercalated cells in the CNT and the CCD are involved in the control of systemic acid-base homeostasis, extracellular fluid volume, and blood pressure (reviewed in refs. [8][9][10]. Pendrin participates in these functions by controlling HCO 3 -secretion and electroneutral Na + -Cl -reabsorption (upon functional coupling with Na + -driven Cl -/HCO 3 -exchanger NDCBE (Slc4a8) (11) and by regulating Na + reabsorption in the adjacent principal cells (12).…”

Decreased Renal Expression of H⁺-ATPase and Pendrin in a Patient with Distal Renal Tubular Acidosis Associated with Sjögren's Syndrome

“…Genetic ablation of pendrin in mice abolishes the luminal chloride-bicarbonate exchanger activity in type B intercalated cells, suggesting that this protein is a component of the apical bicarbonate extruding pathway (7). In order to maintain normal acid-base homeostasis, the expression and activity of pendrin is regulated by the systemic acid-base status, dietary electrolyte intake and hormones, such as angiotensin II and aldosterone (8).…”

Co-Regulated Pendrin and Aquaporin 5 Expression and Trafficking in Type-B Intercalated Cells under Potassium Depletion

“…In the kidney, pendrin is expressed on the apical membrane of type-B intercalated cells in the late distal convoluted tubule (DCT), connecting tubule (CNT) and cortical collecting duct (CCD) and functions mainly as a chloride-bicarbonate exchanger playing a crucial role in acid-base homeostasis [5,6,7]. Specifically, type-B intercalated cells secrete bicarbonate into urine and express V-type H + -ATPases on the basolateral membrane and pendrin on the luminal membrane.…”