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KCNQ1-Dependent Transport in Renal and Gastrointestinal Epithelia

Mutations in the gene encoding for the K+channel $\alpha-subunit$ KCNQ1 have been associated with long QT syndrome and deafness. Besides heart and inner ear epithelial cells, KCNQ1 is expressed in a variety of epithelial cells including renal proximal tubule and gastrointestinal tract epithelial... Full description

1st Person: Grahammer, Florian verfasserin
Additional Persons: Volkl, Harald verfasserin; Pfeifer, Karl verfasserin; Lang, Florian verfasserin
Source: in Proceedings of the National Academy of Sciences of the United States of America Vol. 102, No. 49 (2005), p. 17864-17869
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Type of Publication: Article
Language: English
Published: 2005
Keywords: research-article
K+Channels
H+Secretion
Cl-Secretion
Glucose Transport
Amino Acid Transport
Online: Volltext
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Summary: Mutations in the gene encoding for the K+channel $\alpha-subunit$ KCNQ1 have been associated with long QT syndrome and deafness. Besides heart and inner ear epithelial cells, KCNQ1 is expressed in a variety of epithelial cells including renal proximal tubule and gastrointestinal tract epithelial cells. At these sites, cellular K+ions exit through KCNQ1 channel complexes, which may serve to recycle K+or to maintain cell membrane potential and thus the driving force for electrogenic transepithelial transport, e.g., Na+/glucose cotransport. Employing pharmacologie inhibition and gene knockout, the present study demonstrates the importance of KCNQ1 K+channel complexes for the maintenance of the driving force for proximal tubular and intestinal Na+absorption, gastric acid secretion, and cAMP-induced jejunal Cl-secretion. In the kidney, KCNQ1 appears dispensable under basal conditions because of limited substrate delivery for electrogenic Na+reabsorption to KCNQ1-expressing mid to late proximal tubule. During conditions of increased substrate load, however, luminal KCNQ1 serves to repolarize the proximal tubule and stabilize the driving force for Na+reabsorption. In mice lacking functional KCNQ1, impaired intestinal absorption is associated with reduced serum vitamin B12 concentrations, mild macrocytic anemia, and fecal loss of Na+and K+, the latter affecting K+homeostasis.
Item Description: Copyright: Copyright 2005 National Academy of Sciences of the United States of America
Physical Description: Online-Ressource
ISSN: 0027-8424

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