K ir 1.1 (ROMK) and K v 7.1 (KCNQ1/KvLQT1) are essential for normal gastric acid secretion: importance of functional K ir 1.1

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 K ir 1.1 (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 K ir 1.1 channels are required for gastric acid secretion and that this channel participates with K v 7.1 (KCNQ1/KvLQT1) in the potassium recycling process. We show that K ir 1.1 colocalizes with the β-subunit of H + , K + -ATPase in gastric parietal cells of K ir 1.1 wild-type mice. In K ir 1.1-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 K ir 1.1-deficient as well as barium-blocked wild-type mice. In wild-type mice, both luminal Tertiapin-Q, an inhibitor of K ir 1.1, as well as XE991, an inhibitor of K v 7.1, reduced proton secretion. We propose that K ir 1.1 and K v 7.1 channels collaborate in potassium and current recycling across the apical pole of parietal cells.