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Am J Physiol Cell Physiol. 2015 Aug 15;309(4):C264-70. doi: 10.1152/ajpcell.00012.2015. Epub 2015 Jun 24.

Potassium channel KCNJ15 is required for histamine-stimulated gastric acid secretion.

Author information

  • 1Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China;
  • 2Digestive Diseases and Nutrition Center, Department of Pediatrics, State University of New York at Buffalo, Buffalo, New York; and.
  • 3Department of Medicine, Medical University of South Carolina, Charleston, South Carolina.
  • 4Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Digestive Diseases and Nutrition Center, Department of Pediatrics, State University of New York at Buffalo, Buffalo, New York; and lixinzhu@buffalo.edu.

Abstract

Gastric acid secretion is mediated by the K(+)-dependent proton pump (H(+),K(+)-ATPase), which requires a continuous supply of K(+) at the luminal side of the apical membrane. Several K(+) channels are implicated in gastric acid secretion. However, the identity of the K(+) channel(s) responsible for apical K(+) supply is still elusive. Our previous studies have shown the translocation of KCNJ15 from cytoplasmic vesicles to the apical membrane on stimulation, indicating its involvement in gastric acid secretion. In this study, the stimulation associated trafficking of KCNJ15 was observed in a more native context with a live cell imaging system. KCNJ15 molecules in resting live cells were scattered in cytoplasm but exhibited apical localization after stimulation. Furthermore, knocking down KCNJ15 expression with a short hairpin RNA adenoviral construct abolished histamine-stimulated acid secretion in rabbit primary parietal cells. Moreover, KCNJ15, like H(+),K(+)-ATPase, was detected in all of the parietal cells by immunofluorescence staining, whereas only about half of the parietal cells were positive for KCNQ1 under the same condition. Consistently, the endogenous protein levels of KCNJ15, analyzed by Western blotting, were higher than those of KCNQ1 in the gastric mucosa of human, mouse, and rabbit. These results provide evidence for a major role of KCNJ15 in apical K(+) supply during stimulated acid secretion.

Copyright © 2015 the American Physiological Society.

KEYWORDS:

KCNJ15; gastric acid; parietal cell; potassium; stomach

PMID:
26108660
[PubMed - indexed for MEDLINE]
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