Reduced expression of Na-K-2Cl cotransporter in medullary TAL in vitamin D-induced hypercalcemia in rats.

Abstract

Chronic hypercalcemia (HC) is accompanied by urinary concentration defects, and functional studies indicate defects in the thick ascending limb (TAL). We hypothesize that dysregulation of renal sodium transporters may play an important role in this. Vitamin D-induced HC in rats resulted in polyuria, natriuresis, and phosphaturia. Immunoblotting revealed a marked reduction in the abundance of rat type 1 bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1) in inner stripe of the outer medullary (ISOM; 36 +/- 5%) and whole kidney (51 +/- 11%) in HC. Consistent with this finding, immunocytochemistry and immunoelectron microscopy demonstrated reduced BSC-1 labeling of the apical plasma membrane. Immunoblotting and immunohistochemical labeling of the K channel Kir 1.1 (ROMK) was also reduced in HC. In contrast, there were no reductions in the expression of Na/H exchanger (NHE)3 and Na,K-ATPase in ISOM. The abundance of the proximal tubule type II Na-P(i) cotransporter (NaPi-2) (but not Na,K-ATPase and NHE3) was significantly reduced (25 +/- 4%), consistent with a dramatic increase in urinary phosphate excretion. In conclusion, 1) the reduced abundance of BSC-1 and ROMK in TAL is likely to play a major role in the urinary concentration defects associated with HC and 2) the reduced abundance of NaPi-2 is likely to play a role in the increased urinary phosphate excretion.

• Authors: Weidong Wang, Tae-Hwan Kwon, Chunling Li, Jørgen Frøkiaer, Mark A Knepper, Søren Nielsen
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 282 Issue 1 Pg. F34-44 (Jan 2002) ISSN: 1931-857X [Print] United States
• PMID: 11739110 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Kcnj1 protein, rat
• Phosphates
• Potassium Channels
• Potassium Channels, Inwardly Rectifying
• Slc12a1 protein, rat
• Slc9a3 protein, rat
• Sodium-Hydrogen Exchanger 3
• Sodium-Hydrogen Exchangers
• Sodium-Potassium-Chloride Symporters
• Solute Carrier Family 12, Member 1
• Vitamin D
• Sodium
• Sodium-Potassium-Exchanging ATPase

Topics

• Animals
• Hypercalcemia (chemically induced, metabolism, physiopathology)
• Immunoblotting
• Immunohistochemistry
• Kidney Concentrating Ability (physiology)
• Kidney Medulla (chemistry, physiology, ultrastructure)
• Kidney Tubules, Proximal (chemistry, metabolism, ultrastructure)
• Loop of Henle (chemistry, metabolism, ultrastructure)
• Male
• Microscopy, Immunoelectron
• Natriuresis (physiology)
• Phosphates (metabolism)
• Polyuria (chemically induced, metabolism, physiopathology)
• Potassium Channels (analysis, biosynthesis)
• Potassium Channels, Inwardly Rectifying
• Rats
• Rats, Wistar
• Sodium (metabolism)
• Sodium-Hydrogen Exchanger 3
• Sodium-Hydrogen Exchangers (analysis)
• Sodium-Potassium-Chloride Symporters (analysis, biosynthesis, metabolism)
• Sodium-Potassium-Exchanging ATPase (analysis)
• Solute Carrier Family 12, Member 1
• Vitamin D
• Water-Electrolyte Balance (physiology)