Mice lacking functional KCNQ1 exhibited impaired intestinal absorption, reduced serum vitamin B12, mild macrocytic anemia, and fecal loss of Na+ and K+, highlighting the channel's role in epithelial transport.
Does KCNQ1 knockout or inhibition affect renal and gastrointestinal epithelial transport in mice?
KCNQ1 K+ channel complexes are essential for maintaining the driving force for electrogenic transepithelial transport in renal and gastrointestinal epithelia during increased substrate load.
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 et al. (Mon,) conducted a other in KCNQ1 deficiency (animal model). KCNQ1 gene knockout and pharmacological inhibition vs. Wild-type littermates and vehicle control was evaluated on Renal and gastrointestinal epithelial transport (Na+, K+, Cl-, H+). Mice lacking functional KCNQ1 exhibited impaired intestinal absorption, reduced serum vitamin B12, mild macrocytic anemia, and fecal loss of Na+ and K+, highlighting the channel's role in epithelial transport.