Kir1.1 (ROMK) and Kv7.1 (KCNQ1/KvLQT1) are essential for normal gastric acid secretion: importance of functional Kir1.1.
Kir1.1 (ROMK) and Kv7.1 (KCNQ1/KvLQT1) are essential for normal gastric acid secretion: importance of functional Kir1.1.
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Kir1.1 (ROMK) 和 Kv7.1 (KCNQ1/KvLQT1) 对于正常胃酸分泌至关重要：功能性 Kir1.1 的重要性。
DOI：
10.1007/s00424-014-1593-0
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Geibel,JohnP
中科院分区：
文献类型：
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作者：
Vucic,Esad;Alfadda,Tariq;MacGregor,GordonG;Dong,Ke;Wang,Tong;Geibel,JohnP
钾离子通道是通过胃H+，K+-ATP酶提供细胞外K+与质子交换的顶端渗漏途径，为抑制胃酸分泌提供了潜在的治疗靶点。Kir1.1（ROMK）钾通道介导的高容量的K+再循环所需的NaCl重吸收在厚升支的肾脏，该通道具有功能和调节特性，非常适合由胃壁细胞的K+再循环。我们在这里报告Kir1.1通道是胃酸分泌所必需的，并且该通道与Kv7.1（KCNQ 1/KvLQT 1）一起参与钾循环过程。Kir1.1野生型小鼠胃壁细胞H+，K+-ATP酶β亚基与Kir1.1共定位。在Kir1.1缺陷小鼠，胃粘膜形态，以及壁细胞数量，增殖指数，和超微结构是正常的，但促分泌素刺激的胃酸分泌在整个胃和灌流胃腺是缺席。钾恢复的酸分泌在Kir1.1缺陷以及钡阻断的野生型小鼠的灌注胃腺中的管腔应用。在野生型小鼠中，Kir1.1的抑制剂Luminal Tertiapin-Q以及Kv7.1的抑制剂XE 991都减少了质子分泌。我们建议，Kir1.1和Kv7.1通道合作，跨顶极壁细胞的钾和电流循环。
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.