The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice.
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The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice. / Leviel, Françoise; Hübner, Christian; Houillier, Pascal; Morla, Luciana; Soumaya, El Moghrabi; Brideau, Gaëlle; Hatim, Hassan; Parker, Mark D; Kurth, Ingo; Kougioumtzes, Alexandra; Sinning, Anne; Pech, Vladimir; Riemondy, Kent A; Miller, R Lance; Hummler, Edith; Shull, Gary E; Aronson, Peter S; Doucet, Alain; Wall, Susan M; Chambrey, Régine; Eladari, Dominique.
in: J CLIN INVEST, Jahrgang 120, Nr. 5, 5, 2010, S. 1627-1635.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice.
AU - Leviel, Françoise
AU - Hübner, Christian
AU - Houillier, Pascal
AU - Morla, Luciana
AU - Soumaya, El Moghrabi
AU - Brideau, Gaëlle
AU - Hatim, Hassan
AU - Parker, Mark D
AU - Kurth, Ingo
AU - Kougioumtzes, Alexandra
AU - Sinning, Anne
AU - Pech, Vladimir
AU - Riemondy, Kent A
AU - Miller, R Lance
AU - Hummler, Edith
AU - Shull, Gary E
AU - Aronson, Peter S
AU - Doucet, Alain
AU - Wall, Susan M
AU - Chambrey, Régine
AU - Eladari, Dominique
PY - 2010
Y1 - 2010
N2 - Regulation of sodium balance is a critical factor in the maintenance of euvolemia, and dysregulation of renal sodium excretion results in disorders of altered intravascular volume, such as hypertension. The amiloride-sensitive epithelial sodium channel (ENaC) is thought to be the only mechanism for sodium transport in the cortical collecting duct (CCD) of the kidney. However, it has been found that much of the sodium absorption in the CCD is actually amiloride insensitive and sensitive to thiazide diuretics, which also block the Na-Cl cotransporter (NCC) located in the distal convoluted tubule. In this study, we have demonstrated the presence of electroneutral, amiloride-resistant, thiazide-sensitive, transepithelial NaCl absorption in mouse CCDs, which persists even with genetic disruption of ENaC. Furthermore, hydrochlorothiazide (HCTZ) increased excretion of Na+ and Cl- in mice devoid of the thiazide target NCC, suggesting that an additional mechanism might account for this effect. Studies on isolated CCDs suggested that the parallel action of the Na+-driven Cl-/HCO3- exchanger (NDCBE/SLC4A8) and the Na+-independent Cl-/HCO3- exchanger (pendrin/SLC26A4) accounted for the electroneutral thiazide-sensitive sodium transport. Furthermore, genetic ablation of SLC4A8 abolished thiazide-sensitive NaCl transport in the CCD. These studies establish what we believe to be a novel role for NDCBE in mediating substantial Na+ reabsorption in the CCD and suggest a role for this transporter in the regulation of fluid homeostasis in mice.
AB - Regulation of sodium balance is a critical factor in the maintenance of euvolemia, and dysregulation of renal sodium excretion results in disorders of altered intravascular volume, such as hypertension. The amiloride-sensitive epithelial sodium channel (ENaC) is thought to be the only mechanism for sodium transport in the cortical collecting duct (CCD) of the kidney. However, it has been found that much of the sodium absorption in the CCD is actually amiloride insensitive and sensitive to thiazide diuretics, which also block the Na-Cl cotransporter (NCC) located in the distal convoluted tubule. In this study, we have demonstrated the presence of electroneutral, amiloride-resistant, thiazide-sensitive, transepithelial NaCl absorption in mouse CCDs, which persists even with genetic disruption of ENaC. Furthermore, hydrochlorothiazide (HCTZ) increased excretion of Na+ and Cl- in mice devoid of the thiazide target NCC, suggesting that an additional mechanism might account for this effect. Studies on isolated CCDs suggested that the parallel action of the Na+-driven Cl-/HCO3- exchanger (NDCBE/SLC4A8) and the Na+-independent Cl-/HCO3- exchanger (pendrin/SLC26A4) accounted for the electroneutral thiazide-sensitive sodium transport. Furthermore, genetic ablation of SLC4A8 abolished thiazide-sensitive NaCl transport in the CCD. These studies establish what we believe to be a novel role for NDCBE in mediating substantial Na+ reabsorption in the CCD and suggest a role for this transporter in the regulation of fluid homeostasis in mice.
KW - Animals
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Models, Biological
KW - Kidney metabolism
KW - Mice, Transgenic
KW - Electrophysiology methods
KW - Amiloride pharmacology
KW - Chloride-Bicarbonate Antiporters metabolism
KW - Hydrochlorothiazide pharmacology
KW - Kidney Tubules, Collecting metabolism
KW - Oocytes metabolism
KW - Sodium chemistry
KW - Sodium Chloride Symporter Inhibitors pharmacology
KW - Sodium-Bicarbonate Symporters metabolism
KW - Xenopus
KW - Animals
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Models, Biological
KW - Kidney metabolism
KW - Mice, Transgenic
KW - Electrophysiology methods
KW - Amiloride pharmacology
KW - Chloride-Bicarbonate Antiporters metabolism
KW - Hydrochlorothiazide pharmacology
KW - Kidney Tubules, Collecting metabolism
KW - Oocytes metabolism
KW - Sodium chemistry
KW - Sodium Chloride Symporter Inhibitors pharmacology
KW - Sodium-Bicarbonate Symporters metabolism
KW - Xenopus
M3 - SCORING: Zeitschriftenaufsatz
VL - 120
SP - 1627
EP - 1635
JO - J CLIN INVEST
JF - J CLIN INVEST
SN - 0021-9738
IS - 5
M1 - 5
ER -
