Cortical distal nephron Cl− transport in volume homeostasis and blood pressure regulation
SM Wall, AM Weinstein - American Journal of Physiology …, 2013 - journals.physiology.org
SM Wall, AM Weinstein
American Journal of Physiology-Renal Physiology, 2013•journals.physiology.orgRenal 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 …
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 …
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.
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