title: Kir1.1 (ROMK) and Kv7.1 (KCNQ1/KvLQT1) are essential for normal gastric acid secretion: importance of functional Kir1.1.
abstract: Potassium channels comprise the apical leak pathway supplying extracellular K(+) for exchange with protons by the gastric H(+), K(+)-ATPase and provide potential therapeutic targets for inhibiting gastric acid secretion. The Kir1.1 (ROMK) potassium channel mediates the high capacity K(+) recycling necessary for NaCl reabsorption in the thick ascending limb of the kidney, and this channel exhibits functional and regulatory characteristic well suited for K(+) recycling by gastric parietal cells. We report here that Kir1.1 channels are required for gastric acid secretion and that this channel participates with Kv7.1 (KCNQ1/KvLQT1) in the potassium recycling process. We show that Kir1.1 colocalizes with the β-subunit of H(+), K(+)-ATPase in gastric parietal cells of Kir1.1 wild-type mice. In Kir1.1-deficient mice, gastric mucosal morphology, as well as parietal cell number, proliferation index, and ultrastructure were normal but secretagogue-stimulated gastric acid secretion in whole stomach and perfused gastric glands was absent. Luminal application of potassium-restored acid secretion in perfused gastric glands from Kir1.1-deficient as well as barium-blocked wild-type mice. In wild-type mice, both luminal Tertiapin-Q, an inhibitor of Kir1.1, as well as XE991, an inhibitor of Kv7.1, reduced proton secretion. We propose that Kir1.1 and Kv7.1 channels collaborate in potassium and current recycling across the apical pole of parietal cells.
authors.affiliation: Department of Surgery, Yale University School of Medicine, BML, Room 265, New Haven, CT, 06510, USA.
authors.forename: Esad
authors.initials: E
authors.lastname: Vucic
authors.affiliation: Department of Surgery, Yale University School of Medicine, BML, Room 265, New Haven, CT, 06510, USA.
authors.forename: Tariq
authors.initials: T
authors.lastname: Alfadda
authors.affiliation: Department of Cellular and Molecular Physiology, Yale University School of Medicine, CT, New Haven, 06510, USA.
authors.forename: Gordon G
authors.initials: GG
authors.lastname: MacGregor
authors.affiliation: Department of Cellular and Molecular Physiology, Yale University School of Medicine, CT, New Haven, 06510, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Dong
authors.affiliation: Department of Cellular and Molecular Physiology, Yale University School of Medicine, CT, New Haven, 06510, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Surgery, Yale University School of Medicine, BML, Room 265, New Haven, CT, 06510, USA. john.geibel@yale.edu.|Department of Cellular and Molecular Physiology, Yale University School of Medicine, CT, New Haven, 06510, USA. john.geibel@yale.edu.
authors.forename: John P
authors.initials: JP
authors.lastname: Geibel
mesh_terms: D000818:Animals; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D051657:KCNQ1 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D013270:Stomach / Q000166:cytology; D014981:Xenopus
chemical_list: D051657:KCNQ1 Potassium Channel; C510693:Kcnj1 protein, mouse; C496910:Kcnq1 protein, mouse; D024661:Potassium Channels, Inwardly Rectifying