Figure 4.

Scheme of coupled transcellular and paracellular transport pathways in the proximal tubule (A), the thick ascending limb (B) and the collecting duct (C). A, in the proximal tubule, Na⁺ is absorbed through the Na⁺/H⁺ exchanger (NHE3) and the Na⁺/glucose co-transporter localized in the luminal membrane and secreted into the basolateral side through the Na⁺/K⁺-ATPase and the Na⁺/HCO₃⁻ cotransporter (NBC). Additional Na⁺ can permeate through the tight junction (TJ) via the claudin-2 channels. B, in thick ascending limb (TALH), Na⁺, K⁺ and Cl⁻ are absorbed through the luminal membrane Na⁺/K⁺/2Cl⁻ cotransporter (NKCC2); Na⁺ is secreted into the basolateral side via the Na⁺/K⁺-ATPase; Cl⁻ is secreted into the basolateral side via the chloride channel ClCkb/barttin; K⁺ is recycled into the luminal side through the renal outer medullary potassium channel (ROMK). Due to the continuous reabsorption of NaCl, a NaCl gradient develops from basolateral to luminal sides. The tight junction is permeable to Mg⁺⁺ and Ca⁺⁺ through the claudin-16 and -19 channels. C, in the collecting duct, Na⁺ is absorbed through the epithelial sodium channel (ENaC); Na⁺ is secreted into the basolateral side via the Na⁺/K⁺-ATPase; K⁺ is secreted into the luminal side via the renal outer medullary potassium channel (ROMK). Because of the unilateral Na⁺ absorption, a lumen-negative potential develops, which drives Cl⁻ absorption through the tight junction via claudin-4 and -8 channels.