Transcellular movement of organic cations (OCs) and organic anions (OAs) in kidney proximal tubule epithelial cells. Transcellular movement of organic cations (OCs) and organic anions (OAs) in kidney proximal tubule epithelial cells. (A) Transcellular movement of OCs in a kidney proximal tubule epithelial cell. Movement of OCs are facilitated by the negative potential difference within the cell, which is maintained by the basolateral Na+,K+-ATPase (not shown). OCs enter the cell across the basolateral membrane by organic cation transporters (OCTs), such as OCT2. The authors note that OCT2 is also sometimes depicted as an OC exchanger. Secretion across the apical membrane into the lumen occurs by electroneutral exchange with H+ by solute carrier (SLC) transporters, including multidrug and toxin extrusion (MATE) protein 2/2K, and by ATP-binding cassette (ABC) transporters, such as multidrug-resistant protein 1 (MDR1), which use energy generated by ATP hydrolysis to transport molecules across the apical membrane. Only a fraction of the known transporters are shown. (B) OA transport via organic anion transporters (OATs) in a proximal tubule epithelial cell. Primary active transport of sodium out of the cell by the basolateral Na+,K+-ATPase creates the gradient that facilitates sodium dicarboxylate cotransporters (NaDCs) to move sodium and dicarboxylates [R(COO−)2], such as α-ketoglutarate, into the cell. The resulting high intracellular concentration of dicarboxylates promotes uptake of OA across the basolateral membrane in exchange for [R(COO−)2] by organic anion transporters (OAT1 and OAT3). Apical exit involves ABC transporters including multidrug-associated resistance proteins (MRP2, MRP4) and possibly other SLC transporters including OAT4 and urate transporter 1 (URAT1, not shown). Sanjay K. Nigam et al. CJASN 2015;10:2039-2049 ©2015 by American Society of Nephrology