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 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.
Vallon
Volker
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
Grahammer
Florian
F
Volkl
Harald
H
Sandu
Ciprian D
CD
Richter
Kerstin
K
Rexhepaj
Rexhepi
R
Gerlach
Uwe
U
Rong
Qi
Q
Pfeifer
Karl
K
Lang
Florian
F
D000584:Amiloride / Q000494:pharmacology; D000748:Anemia, Macrocytic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001692:Biological Transport; D004847:Epithelial Cells / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D051657:KCNQ1 Potassium Channel / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007677:Kidney Function Tests; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010295:Parietal Cells, Gastric / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013270:Stomach / Q000187:drug effects
D051657:KCNQ1 Potassium Channel; D000584:Amiloride; D012964:Sodium; D005947:Glucose; D011188:Potassium