title: Potassium channel KCNJ15 is required for histamine-stimulated gastric acid secretion.
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.
authors.affiliation: Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China;
authors.forename: Jianye
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Digestive Diseases and Nutrition Center, Department of Pediatrics, State University of New York at Buffalo, Buffalo, New York; and.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Serhan
authors.initials: S
authors.lastname: Karvar
authors.affiliation: Digestive Diseases and Nutrition Center, Department of Pediatrics, State University of New York at Buffalo, Buffalo, New York; and.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Baker
authors.affiliation: Digestive Diseases and Nutrition Center, Department of Pediatrics, State University of New York at Buffalo, Buffalo, New York; and.
authors.forename: Wenjun
authors.initials: W
authors.lastname: He
authors.affiliation: Digestive Diseases and Nutrition Center, Department of Pediatrics, State University of New York at Buffalo, Buffalo, New York; and.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Baker
authors.affiliation: Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China;
authors.forename: Guang
authors.initials: G
authors.lastname: Ji
authors.affiliation: Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China;
authors.forename: Jianqun
authors.initials: J
authors.lastname: Xie
authors.affiliation: Institute 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.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000293:Adolescent; D000818:Animals; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D057809:HEK293 Cells; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D010295:Parietal Cells, Gastric / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis*; D011817:Rabbits
chemical_list: C103861:KCNJ15 protein, human; D024661:Potassium Channels, Inwardly Rectifying; D006632:Histamine
keywords: KCNJ15; gastric acid; parietal cell; potassium; stomach