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Identification of Potassium Channels Associated With H+/K+-Atpase in the Parietal Cell

  • F. Grahammer
  • Herling Aw
  • T. Von Hahn
  • D. Heitzmann
  • H. J. Lang
  • A. Schmitt-Gräff
  • R. Nitschke
  • O. Wittekindt
  • M. Bleich
  • J. Barhanin
  • R. Warth

Summary

Gastric H+ secretion via the H+/K+-ATPase is coupled to the uptake of K+. However, the molecular identity of luminal K+ channels enabling K+ recycling in parietal cells was unknown. Cuppoletti and coworkers presented at this meeting data on Kir2.1 as a K+ channel in the luminal membrane. We identified KCNQ1, which is mutated in cardiac long QT syndrome, as another K+ channel located in tubulo-vesicles and apical membrane compartment of parietal cells, where it co-localized with H+/K+-ATPase in immunofluorescence experiments. Blockade of KCNQ1 current by the chromanol 293B led to complete inhibition of acid secretion in mouse, rat, and dogs in-vivo and in isolated rabbit gastric glands in-vitro. The putative KCNQ1 subunits, KCNE2 and KCNE3, were abundant; KCNE1, however, was absent in human stomach. Co-expression of KCNE3/KCNQ1 in COS cells led to a cAMP- and IP3/Ca2+-activated and acid-insensitive K+ current. In contrast, cAMP, IP3/Ca2+, and low extracellular pH activated KCNE2/KCNQ1. In conclusion, we identified KCNQ1 as a luminal K+ channel in parietal cells. 293B almost completely abolished acid secretion in several species, although Kir2.1, the other putative luminal K+ channel, is unaffected by 293B. Moreover, in KCNQ1 knockout mice gastric acid secretion is impaired (14). These data speak in favor for the crucial role of KCNQ1 during gastric proton secretion. The putative KCNQ1 β-subunits KCNE3 and KCNE2 are expressed in human stomach. One or both are candidates to co-assemble with KCNQ1 in parietal cells to form a luminal K+ channel. Stomach- and subunit-specific inhibitors of KCNQ1 might offer new therapeutical perspectives for peptic ulcer disease.

Keywords

Potassium Channel Acid Secretion Parietal Cell Gastric Acid Secretion Proton Transport 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • F. Grahammer
    • 1
  • Herling Aw
    • 3
  • T. Von Hahn
    • 1
  • D. Heitzmann
    • 1
  • H. J. Lang
    • 3
  • A. Schmitt-Gräff
    • 2
  • R. Nitschke
    • 1
  • O. Wittekindt
    • 1
  • M. Bleich
    • 3
  • J. Barhanin
    • 4
  • R. Warth
    • 4
  1. 1.Institute of PhysiologyAlbert-Ludwigs-UniversityFreiburgGermany
  2. 2.Institute of PathologyAlbert-Ludwigs-UniversityFreiburgGermany
  3. 3.Aventis Pharma GmbHFrankfurt am MainGermany
  4. 4.IPMCCNRSValbonne Sophia AntipolisFrance

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