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Molecular evidence for a role for K(+)-Cl(-) cotransporters in the kidney.
- Source :
-
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2013 Nov 15; Vol. 305 (10), pp. F1402-11. Date of Electronic Publication: 2013 Oct 02. - Publication Year :
- 2013
-
Abstract
- K(+)-Cl(-) cotransporter (KCC) isoforms 3 (KCC3) and 4 (KCC4) are expressed at the basolateral membrane of proximal convoluted tubule cells, and KCC4 is present in the basolateral membrane of the thick ascending loop of Henle's limb and α-intercalated cells of the collecting duct. Little is known, however, about the physiological roles of these transporters in the kidney. We evaluated KCC3 and KCC4 mRNA and protein expression levels and intrarenal distribution in male Wistar rats or C57 mice under five experimental conditions: hyperglycemia after a single dose of streptozotocin, a low-salt diet, metabolic acidosis induced by ammonium chloride in drinking water, and low- or high-K(+) diets. Both KCC3 mRNA and protein expression were increased during hyperglycemia in the renal cortex and at the basolateral membrane of proximal tubule cells but not with a low-salt diet or acidosis. In contrast, KCC4 protein expression was increased by a low-sodium diet in the whole kidney and by metabolic acidosis in the renal outer medulla, specifically at the basolateral membrane of α-intercalated cells. The increased protein expression of KCC4 by a low-salt diet was also observed in WNK4 knockout mice, suggesting that upregulation of KCC4 in these circumstances is not WNK4 dependent. No change in KCC3 or KCC4 protein expression was observed under low- or high-K(+) diets. Our data are consistent with a role for KCC3 in the proximal tubule glucose reabsorption mechanism and for KCC4 in salt reabsorption of the thick ascending loop of Henle's loop and acid secretion of the collecting duct.
- Subjects :
- Acidosis chemically induced
Acidosis metabolism
Ammonium Chloride
Animals
Biological Transport
Blood Glucose metabolism
Diet, Sodium-Restricted
Disease Models, Animal
Gene Expression Regulation
Hydrogen-Ion Concentration
Hyperglycemia chemically induced
Hyperglycemia metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Potassium, Dietary metabolism
Protein Serine-Threonine Kinases genetics
Protein Serine-Threonine Kinases metabolism
RNA, Messenger metabolism
Rats
Rats, Wistar
Sodium Chloride, Dietary metabolism
Streptozocin
Symporters genetics
Kidney metabolism
Symporters metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1466
- Volume :
- 305
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Renal physiology
- Publication Type :
- Academic Journal
- Accession number :
- 24089410
- Full Text :
- https://doi.org/10.1152/ajprenal.00390.2013