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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Rexhepaj, Rexhepi Gerlach, Uwe Richter, Kerstin Volkl, Harald Rong, Qi Lang, Florian Sandu, Ciprian D. Vallon, Volker Pfeifer, Karl Grahammer, Florian |
| Description | Author Affiliation: Vallon V ( Department of Medicine, University of California at San Diego and Veterans Affairs San Diego Health Care System, San Diego, CA 92161, USA. vvallon@ucsd.edu); |
| Abstract | 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 pharmacologic 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 49 |
| Volume Number | 102 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2005-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Epithelial Cells Metabolism Intestines KCNQ1 Potassium Channel Kidney Stomach Amiloride Pharmacology Anemia, Macrocytic Genetics Pathology Animals Biological Transport Glucose Hydrogen-Ion Concentration Drug Effects Deficiency Kidney Function Tests Mice Mice, Knockout Parietal Cells, Gastric Potassium Sodium Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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