Kir4.1 Channel Expression Is Essential for Parietal Cell Control of Acid Secretion
Kir4.1 Channel Expression Is Essential for Parietal Cell Control of Acid Secretion
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Kir4.1 通道表达对于壁细胞控制酸分泌至关重要
DOI：
10.1074/jbc.m110.151191
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发表时间：
2011-04-22
影响因子：
4.8
通讯作者：
Seidler, Ursula
中科院分区：
文献类型：
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作者：
Song, Penghong;Groos, Stephanie;Seidler, Ursula
研究发现，在壁细胞（PC）的整个泌酸周期中，Kir4.1通道与H⁺/K⁺ -ATP酶共定位。本研究旨在探究它们的功能作用。对7 - 8日龄的Kir4.1基因敲除小鼠及其野生型同窝小鼠的胃黏膜，测定其泌酸速率、电生理参数、壁细胞超微结构以及基因和蛋白质表达情况。与野生型胃黏膜相比，Kir4.1基因敲除小鼠（Kir4.1⁻/⁻）的胃黏膜分泌的酸显著增多，且起始分泌的速度明显更快。壁细胞数量未见变化，但观察到H⁺/K⁺ -ATP酶基因和蛋白质表达相对上调（而其他壁细胞离子转运体无此变化）。电子显微镜显示，静止状态下Kir4.1⁻/⁻壁细胞的微管泡膜完全融合且缺乏微管泡，这表明敲除Kir4.1基因可能也会干扰微管泡的内吞作用。因此，这种内向整流钾通道在壁细胞顶膜中的作用可能是平衡通过KCNQ1/KCNE2外流的钾离子与H⁺/K⁺ -ATP酶缓慢周转所重吸收的钾离子，进而对钾离子重吸收、胃酸分泌抑制以及膜循环产生影响。我们的研究结果表明，Kir4.1通道参与胃酸分泌的调控，且可能对分泌膜循环也有影响。胃酸分泌的调节需要
Kir4.1 channels were found to colocalize with the H+/K+ ATPase throughout the parietal cell (PC) acid secretory cycle. This study was undertaken to explore their functional role. Acid secretory rates, electrophysiological parameters, PC ultrastructure, and gene and protein expression were determined in gastric mucosae of 7-8-day-old Kir4.1-deficient mice and WT littermates. Kir4.1(-/-) mucosa secreted significantly more acid and initiated secretion significantly faster than WT mucosa. No change in PC number but a relative up-regulation of H+/K+ ATPase gene and protein expression (but not of other PC ion transporters) was observed. Electron microscopy revealed fully fused canalicular membranes and a lack of tubulovesicles in resting state Kir4.1(-/-) PCs, suggesting that Kir4.1 ablation may also interfere with tubulovesicle endocytosis. The role of this inward rectifier in the PC apical membrane may therefore be to balance between K+ loss via KCNQ1/KCNE2 and K+ reabsorption by the slow turnover of the H+/K+-ATPase, with consequences for K+ reabsorption, inhibition of acid secretion, and membrane recycling. Our results demonstrate that Kir4.1 channels are involved in the control of acid secretion and suggest that they may also affect secretory membrane recycling. The regulation of gastric acid secretion requires