Miller Marian L, Judd Louise M, Van Driel Ian R, Andringa Anastasia, Flagella Michael, Bell Sheila M, Schultheis Patrick J, Spicer Zachary, Shull Gary E
Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, 3223 Eden Avenue, Cincinnati, OH 45267-0056, USA.
Cell Tissue Res. 2002 Sep;309(3):369-80. doi: 10.1007/s00441-002-0606-z. Epub 2002 Jul 30.
Ion transporters play a central role in gastric acid secretion. To determine whether some of these transporters are necessary for the normal ultrastructure of secretory membranes in gastric parietal cells, mice lacking transporters for H+, K+, Cl-, and Na+ were examined for alterations in volume density (Vd) of basolateral, apical, tubulovesicular and canalicular membranes, microvillar dimensions, membrane flexibility, and ultrastructure. In mice lacking Na+/H+ exchanger 1 (NHE1) or the Na+-K+-2Cl- cotransporter (NKCC1), the ultrastructure and Vd of secretory membranes and the secretory canalicular to tubulovesicular membrane ratio (SC/TV), a morphological correlate of secretory activity, were similar to those of wild-type mice. In mice lacking Na+/H+ exchanger 2 (NHE2) or gastric H+, K+ -ATPase alpha- or beta-subunits, the SC/TV ratio and Vd of secretory membranes were decreased, though canaliculi were often dilated. In H+, K+ -ATPase-deficient parietal cells, canalicular folds were decreased, normally abundant tubulovesicles were replaced with a few rigid round vesicles, and microvilli were sparse, stiff and short, in contrast to the long and flexible microvilli in wild-type cells. In addition, microvilli of the H+, K+ -ATPase-deficient parietal cells had centrally bundled F-actin filaments, unlike the microvilli of wild-type cells, in which actin filaments were peripherally positioned concentric to the plasmalemma. Data showed that the absence of H+, K+ -ATPase produced fundamental changes in parietal cell membrane ultrastructure, suggesting that the pump provides an essential link between the membranes and F-actin, critical to the gross architecture and suppleness of the secretory membranes.
离子转运体在胃酸分泌中起核心作用。为了确定其中一些转运体对于胃壁细胞分泌膜的正常超微结构是否必要，对缺乏H⁺、K⁺、Cl⁻和Na⁺转运体的小鼠进行了检查，观察其基底外侧膜、顶端膜、微管泡膜和小管膜的体积密度（Vd）变化、微绒毛尺寸、膜柔韧性和超微结构。在缺乏钠氢交换体1（NHE1）或钠钾氯共转运体（NKCC1）的小鼠中，分泌膜的超微结构和Vd以及分泌小管与微管泡膜比率（SC/TV）（分泌活性的形态学相关指标）与野生型小鼠相似。在缺乏钠氢交换体2（NHE2）或胃H⁺，K⁺ -ATP酶α或β亚基的小鼠中，分泌膜的SC/TV比率和Vd降低，尽管小管常常扩张。在H⁺，K⁺ -ATP酶缺陷的壁细胞中，小管褶皱减少，通常丰富的微管泡被一些刚性圆形囊泡取代，微绒毛稀疏、僵硬且短小，这与野生型细胞中长而柔韧的微绒毛形成对比。此外，H⁺，K⁺ -ATP酶缺陷的壁细胞的微绒毛有集中成束的F-肌动蛋白丝，这与野生型细胞的微绒毛不同，野生型细胞的肌动蛋白丝位于质膜周围呈同心状。数据表明，H⁺，K⁺ -ATP酶的缺失导致壁细胞膜超微结构发生根本变化，提示该泵提供了膜与F-肌动蛋白之间的关键联系，这对分泌膜的总体结构和柔韧性至关重要。
