title: Mechanisms of chloride transport in the proximal tubule.
abstract: The major fraction of filtered Cl- is reabsorbed in the proximal tubule. An important component of Cl- reabsorption is passive and paracellular, driven by the lumen-negative potential difference in the early proximal tubule and the outwardly directed concentration gradient for Cl- in the later proximal tubule. Evidence suggests that a significant additional component of NaCl reabsorption in the proximal tubule is active and transcellular. Cl-/formate and Cl-/oxalate exchangers have been identified as mechanisms of uphill Cl- entry across the apical membrane. For steady-state Cl- absorption to occur by these mechanisms, formate and oxalate must recycle from lumen to cell. Recent studies indicate that recycling of formate occurs by H(+)-coupled formate transport in parallel with Na+/H+ exchange, whereas oxalate recycling takes place by oxalate/sulfate exchange in parallel with Na(+)-sulfate cotransport. The predominant route for Cl- exit across the basolateral membrane is via Cl- channels. Unresolved issues include the adequacy of formate recycling to sustain Cl- absorption by Cl-/formate exchange, the existence and contributions of additional mechanisms for apical Cl entry and basolateral Cl- exit, and the relative magnitudes of transcellular and paracellular transport under physiological conditions. In addition, the molecular identification and mechanisms of regulation of the Cl-/formate and Cl-/oxalate exchangers remain to be defined.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8029, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Aronson
authors.forename: G
authors.initials: G
authors.lastname: Giebisch
mesh_terms: D000818:Animals; D000838:Anions / Q000378:metabolism; D017920:Antiporters / Q000378:metabolism; D001692:Biological Transport; D001693:Biological Transport, Active; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides / Q000378:metabolism*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism
chemical_list: D000838:Anions; D017920:Antiporters; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides