Chloride transport in the renal proximal tubule

The renal proximal tubule is responsible for most of the renal sodium, chloride, and bicarbonate reabsorption. Micropuncture studies and electrophysiological techniques have furnished the bulk of our knowledge about the physiology of this tubular segment. As a consequence of the leakiness of this epithelium, paracellular ionic transport—in particular that of Cl−—is of considerable importance in this first part of the nephron. It was long accepted that proximal Cl− reabsorption proceeds solely paracellularly, but it is now known that transcellular Cl− transport also exists. Cl− channels and Cl−-coupled transporters are involved in transcellular Cl− transport. In the apical membrane, Cl−/anion (formate, oxalate and bicarbonate) exchangers represent the first step in transcellular Cl− reabsorption. A basolateral Cl−/HCO3− exchanger, involved in HCO3− reclamation, participates in the rise of intracellular Cl− activity above its equilibrium value, and thus also contributes to the creation of an outwardly directed electrochemical Cl− gradient across the cell membranes. This driving force favours Cl− diffusion from the cell to the lumen and to the interstitium. In the basolateral membrane, the main mechanism for transcellular Cl− reabsorption is a Cl− conductance, but a Na+-driven Cl−/HCO3− exchanger may also participate in Cl− reabsorption.