title: Cortical distal nephron Cl(-) transport in volume homeostasis and blood pressure regulation.
abstract: Renal intercalated cells mediate the secretion or absorption of Cl(-) and OH(-)/H(+) equivalents in the connecting segment (CNT) and cortical collecting duct (CCD). In so doing, they regulate acid-base balance, vascular volume, and blood pressure. Cl(-) absorption is either electrogenic and amiloride-sensitive or electroneutral and thiazide-sensitive. However, which Cl(-) transporter(s) are targeted by these diuretics is debated. While epithelial Na(+) channel (ENaC) does not transport Cl(-), it modulates Cl(-) transport probably by generating a lumen-negative voltage, which drives Cl(-) flux across tight junctions. In addition, recent evidence indicates that ENaC inhibition increases electrogenic Cl(-) secretion via a type A intercalated cells. During ENaC blockade, Cl(-) is taken up across the basolateral membrane through the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) and then secreted across the apical membrane through a conductive pathway (a Cl(-) channel or an electrogenic exchanger). The mechanism of this apical Cl(-) secretion is unresolved. In contrast, thiazide diuretics inhibit electroneutral Cl(-) absorption mediated by a Na(+)-dependent Cl(-)/HCO3(-) exchanger. The relative contribution of the thiazide and the amiloride-sensitive components of Cl(-) absorption varies between studies and probably depends on the treatment model employed. Cl(-) absorption increases markedly with angiotensin and aldosterone administration, largely by upregulating the Na(+)-independent Cl(-)/HCO3(-) exchanger pendrin. In the absence of pendrin [Slc26a4((-/-)) or pendrin null mice], aldosterone-stimulated Cl(-) absorption is significantly reduced, which attenuates the pressor response to this steroid hormone. Pendrin also modulates aldosterone-induced changes in ENaC abundance and function through a kidney-specific mechanism that does not involve changes in the concentration of a circulating hormone. Instead, pendrin changes ENaC abundance and function, at least in part, by altering luminal HCO3(-). This review summarizes mechanisms of Cl(-) transport in CNT and CCD and how these transporters contribute to the regulation of extracellular volume and blood pressure.
authors: Renal Division, WMB Rm. 338, 1639 Pierce Dr., NE, Atlanta, GA 30322. smwall@emory.edu.
authors: Susan M
authors: SM
authors: Wall
authors: Alan M
authors: AM
authors: Weinstein
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism*; D004232:Diuretics / Q000494:pharmacology; D053503:Epithelial Sodium Channels / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000502:physiology; D009399:Nephrons / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000378:metabolism
chemical_list: D027321:Anion Transport Proteins; D018118:Chloride Channels; D002712:Chlorides; D004232:Diuretics; D053503:Epithelial Sodium Channels; D012964:Sodium
keywords: Cl-/HCO3- exchange; ENaC; Pds; Slc26a4; blood pressure; intercalated cells; pendrin
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