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J Am Soc Nephrol
2010 Nov 01;2111:1928-41. doi: 10.1681/ASN.2009121257.
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Pendrin modulates ENaC function by changing luminal HCO3-.
Pech V, Pham TD, Hong S, Weinstein AM, Spencer KB, Duke BJ, Walp E, Kim YH, Sutliff RL, Bao HF, Eaton DC, Wall SM.
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The epithelial Na(+) channel, ENaC, and the Cl(-)/HCO(3)(-) exchanger, pendrin, mediate NaCl absorption within the cortical collecting duct and the connecting tubule. Although pendrin and ENaC localize to different cell types, ENaC subunit abundance and activity are lower in aldosterone-treated pendrin-null mice relative to wild-type mice. Because pendrin mediates HCO(3)(-) secretion, we asked if increasing distal delivery of HCO(3)(-) through a pendrin-independent mechanism "rescues" ENaC function in pendrin-null mice. We gave aldosterone and NaHCO(3) to increase pendrin-dependent HCO(3)(-) secretion within the connecting tubule and cortical collecting duct, or gave aldosterone and NaHCO(3) plus acetazolamide to increase luminal HCO(3)(-) concentration, [HCO(3)(-)], independent of pendrin. Following treatment with aldosterone and NaHCO(3), pendrin-null mice had lower urinary pH and [HCO(3)(-)] as well as lower renal ENaC abundance and function than wild-type mice. With the addition of acetazolamide, however, acid-base balance as well as ENaC subunit abundance and function was similar in pendrin-null and wild-type mice. We explored whether [HCO(3)(-)] directly alters ENaC abundance and function in cultured mouse principal cells (mpkCCD). Amiloride-sensitive current and ENaC abundance rose with increased [HCO(3)(-)] on the apical or the basolateral side, independent of the substituting anion. However, ENaC was more sensitive to changes in [HCO(3)(-)] on the basolateral side of the monolayer. Moreover, increasing [HCO(3)(-)] on the apical and basolateral side of Xenopus kidney cells increased both ENaC channel density and channel activity. We conclude that pendrin modulates ENaC abundance and function, at least in part by increasing luminal [HCO(3)(-)] and/or pH.
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Bailey,
NHE2-mediated bicarbonate reabsorption in the distal tubule of NHE3 null mice.
2004, Pubmed
Bailey,
NHE2-mediated bicarbonate reabsorption in the distal tubule of NHE3 null mice.
2004,
Pubmed Bens,
Corticosteroid-dependent sodium transport in a novel immortalized mouse collecting duct principal cell line.
1999,
Pubmed Boudry,
Effect of acid lumen pH on potassium transport in renal cortical collecting tubules.
1976,
Pubmed Brooks,
Targeted proteomic profiling of renal Na(+) transporter and channel abundances in angiotensin II type 1a receptor knockout mice.
2002,
Pubmed Buerkert,
Segmental analysis of the renal tubule in buffer production and net acid formation.
1983,
Pubmed Catalán,
Cftr and ENaC ion channels mediate NaCl absorption in the mouse submandibular gland.
2010,
Pubmed Chang,
Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1.
1996,
Pubmed Collier,
Extracellular chloride regulates the epithelial sodium channel.
2009,
Pubmed
,
Xenbase DuBose,
Effect of carbonic anhydrase inhibition on superficial and deep nephron bicarbonate reabsorption in the rat.
1983,
Pubmed Everett,
Targeted disruption of mouse Pds provides insight about the inner-ear defects encountered in Pendred syndrome.
2001,
Pubmed Faroqui,
Metabolic acidosis has dual effects on sodium handling by rat kidney.
2006,
Pubmed Frische,
Regulated expression of pendrin in rat kidney in response to chronic NH4Cl or NaHCO3 loading.
2003,
Pubmed Hallows,
Regulation of epithelial Na+ transport by soluble adenylyl cyclase in kidney collecting duct cells.
2009,
Pubmed
,
Xenbase Hanley,
Study of chloride transport across the rabbit cortical collecting tubule.
1978,
Pubmed Kemendy,
Aldosterone alters the open probability of amiloride-blockable sodium channels in A6 epithelia.
1992,
Pubmed Kim,
Long-term regulation of renal Na-dependent cotransporters and ENaC: response to altered acid-base intake.
2000,
Pubmed Kim,
Immunocytochemical localization of pendrin in intercalated cell subtypes in rat and mouse kidney.
2002,
Pubmed Kim,
Intercalated cell H+/OH- transporter expression is reduced in Slc26a4 null mice.
2005,
Pubmed Kim,
Reduced ENaC protein abundance contributes to the lower blood pressure observed in pendrin-null mice.
2007,
Pubmed Knepper,
Organization of nephron function.
1983,
Pubmed Marunaka,
Effects of vasopressin and cAMP on single amiloride-blockable Na channels.
1991,
Pubmed Masilamani,
Aldosterone-mediated regulation of ENaC alpha, beta, and gamma subunit proteins in rat kidney.
1999,
Pubmed Milton,
Regulation of B-type intercalated cell apical anion exchange activity by CO2/HCO3-.
1998,
Pubmed Palmer,
Effects of cell Ca and pH on Na channels from rat cortical collecting tubule.
1987,
Pubmed Pech,
Angiotensin II increases chloride absorption in the cortical collecting duct in mice through a pendrin-dependent mechanism.
2007,
Pubmed Richardson,
Bicarbonate reabsorption in the papillary collecting duct: effect of acetazolamide.
1982,
Pubmed Royaux,
Pendrin, encoded by the Pendred syndrome gene, resides in the apical region of renal intercalated cells and mediates bicarbonate secretion.
2001,
Pubmed Schuster,
Cyclic adenosine monophosphate-stimulated anion transport in rabbit cortical collecting duct. Kinetics, stoichiometry, and conductive pathways.
1986,
Pubmed Shimkets,
Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel.
1994,
Pubmed Shipway,
Biochemical characterization of prostasin, a channel activating protease.
2004,
Pubmed Snyder,
Minireview: regulation of epithelial Na+ channel trafficking.
2005,
Pubmed Stanton,
Effects of pH on potassium transport by renal distal tubule.
1982,
Pubmed Sun,
Decreased expression of Slc26a4 (Pendrin) and Slc26a7 in the kidneys of carbonic anhydrase II-deficient mice.
2008,
Pubmed Terris,
Long-term regulation of four renal aquaporins in rats.
1996,
Pubmed Verlander,
Dietary Cl(-) restriction upregulates pendrin expression within the apical plasma membrane of type B intercalated cells.
2006,
Pubmed Verlander,
Deoxycorticosterone upregulates PDS (Slc26a4) in mouse kidney: role of pendrin in mineralocorticoid-induced hypertension.
2003,
Pubmed Wall,
Localization of pendrin in mouse kidney.
2003,
Pubmed Wall,
Hypotension in NKCC1 null mice: role of the kidneys.
2006,
Pubmed Wall,
NaCl restriction upregulates renal Slc26a4 through subcellular redistribution: role in Cl- conservation.
2004,
Pubmed Wall,
NH+4 augments net acid secretion by a ouabain-sensitive mechanism in isolated perfused inner medullary collecting ducts.
1996,
Pubmed Weinstein,
A mathematical model of distal nephron acidification: diuretic effects.
2008,
Pubmed Yao,
Mice lacking protein kinase C beta present modest increases in systolic blood pressure and NH4Cl-induced metabolic acidosis.
2006,
Pubmed
