Document Detail


Functional up-regulation of basolateral Na+-dependent HCO3- transporter NBCn1 in medullary thick ascending limb of K+-depleted rats.
MedLine Citation:
PMID:  15316781     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The electroneutral, Na(+)-coupled HCO(3)(-) co-transporter (NBCn1) is expressed in the basolateral membrane of rat medullary thick ascending limb (mTAL) segments and is up-regulated strongly during metabolic acidosis. We have suggested previously that NBCn1-mediated HCO(3)(-) uptake across the basolateral cell membrane is an important buffering mechanism during the transcellular transport of NH(4)(+) in the mTAL. To investigate this further we treated rats with a low-K(+) diet for 4 days, a manoeuvre known to increase proximal tubular ammoniagenesis and delivery of luminal NH(4)(+) to the mTAL. Hypokalaemia strongly increased immunolabelling of basolateral NBCn1 in the mTAL of the inner stripe of the outer medulla. Immunoblotting revealed an eightfold up-regulation of NBCn1 protein in K(+)-depleted rats. Subsequently we used in vitro perfusion of isolated mTAL and BCECF imaging to investigate Na(+)-coupled HCO(3)(-) influx in normal and K(+)-depleted rats. Hypokalaemia induced a threefold up-regulation of Na(+)-coupled HCO(3)(-) influx (1.64+/-0.28 vs. 0.47+/-0.05 pH units/minute, n=8). The Na(+)-dependent alkalinization was also significantly larger in K(+)-depleted rats (0.38+/-0.04 vs. 0.23+/-0.03 pH units). These data indicate that K(+)-depleted rats respond with a strong up-regulation of NBCn1 protein and function, probably to cope with the higher tubular load of NH(4)(+), and strengthen our previous suggestion that NBCn1 is an important player in the excretion of NH(4)(+). They also indicate that it is the delivery of luminal NH(4)(+) rather than systemic changes of pH that determine the expression of NBCn1.
Authors:
Jakob K Jakobsen; Elvin Odgaard; Weidong Wang; Marie Louise Elkjaer; Søren Nielsen; Christian Aalkjaer; Jens Leipziger
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-08-13
Journal Detail:
Title:  Pflügers Archiv : European journal of physiology     Volume:  448     ISSN:  0031-6768     ISO Abbreviation:  Pflugers Arch.     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-11-01     Completed Date:  2005-06-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0154720     Medline TA:  Pflugers Arch     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  571-8     Citation Subset:  IM    
Affiliation:
Institute of Physiology, University of Aarhus, Olé Worms Allé 160, 8000 Aarhus C, Denmark.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bicarbonates / metabolism
Blotting, Western
Diet
Female
Immunohistochemistry
Kidney Medulla / metabolism*
Loop of Henle / metabolism*
Potassium / metabolism*
Quaternary Ammonium Compounds / metabolism*
Rats
Rats, Wistar
Sodium-Bicarbonate Symporters / biosynthesis*
Up-Regulation
Chemical
Reg. No./Substance:
0/Bicarbonates; 0/Quaternary Ammonium Compounds; 0/Slc4a4 protein, rat; 0/Sodium-Bicarbonate Symporters; 7440-09-7/Potassium

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