title: KCNQ1-dependent transport in renal and gastrointestinal epithelia.
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.
authors.affiliation: 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
authors.forename: Volker
authors.initials: V
authors.lastname: Vallon
authors.forename: Florian
authors.initials: F
authors.lastname: Grahammer
authors.forename: Harald
authors.initials: H
authors.lastname: Volkl
authors.forename: Ciprian D
authors.initials: CD
authors.lastname: Sandu
authors.forename: Kerstin
authors.initials: K
authors.lastname: Richter
authors.forename: Rexhepi
authors.initials: R
authors.lastname: Rexhepaj
authors.forename: Uwe
authors.initials: U
authors.lastname: Gerlach
authors.forename: Qi
authors.initials: Q
authors.lastname: Rong
authors.forename: Karl
authors.initials: K
authors.lastname: Pfeifer
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: 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
chemical_list: D051657:KCNQ1 Potassium Channel; D000584:Amiloride; D012964:Sodium; D005947:Glucose; D011188:Potassium