Schwab A, Oberleithner H
Physiologisches Institut, Würzburg, Germany.
Pflugers Arch. 1996;432(3 Suppl):R87-93.
In this article we review aspects of plasticity of renal epithelial cells. We focus on one particular feature, namely on cell migration. For normal renal and other epithelial cells migration is a motif of plasticity which can be activated after disrupture of epithelial integrity. In the case of transformed renal epithelial cells, however, migration is "pathophysiological" as it is no longer regulated as in normal cells. We studied migration in a permanently transformed Madin-Darby canine kidney cell line, called MDCK-F. Locomotion of these cells strictly depends-in addition to the cytoskeletal "migration machinery"-upon the oscillatory activity of a Ca(2+)-sensitive plasma membrane K+ channel. We propose that K+ channel activity is linked to migration via changes of cell volume. We deduced from patch-clamp experiments in combination with high resolution 3D-images obtained by atomic force microscopy that periods of high K+ channel activity are parallelled by cell shrinkage. By locally superfusing either cell body (rear part) or lamellipodium (front part of the cell) with specific K+ channel blockers we disclosed a polar distribution of K+ channel activity in MDCK-F cells. K+ channels are preferentially active at the rear part of MDCK-F cells. We discuss how localized K+ channel activity, in concert with other migration-relevant phenomena such as "tail contraction" or asymmetric cell-matrix interactions, may result in localized changes of cell volume supporting migration. Finally, we define cell polarization for a migrating epithelial cell. Whereas normal epithelial cells are "vertically" polarized, transformed cells are "horizontally" polarized, i.e., in the plane of movement. Such a distinct view could be helpful for better understanding the transition from a normal differentiated epithelial cell to a tumorigenic migrating cell.
在本文中，我们回顾了肾上皮细胞可塑性的各个方面。我们聚焦于一个特定特征，即细胞迁移。对于正常肾上皮细胞和其他上皮细胞而言，迁移是可塑性的一个特征，上皮完整性破坏后该特征可被激活。然而，对于转化的肾上皮细胞，迁移是“病理生理的”，因为它不再像正常细胞那样受到调控。我们研究了一种永久转化的犬肾细胞系（称为MDCK - F）中的迁移情况。这些细胞的运动除了依赖细胞骨架的“迁移机制”外，还严格取决于一种钙敏感质膜钾通道的振荡活性。我们提出钾通道活性通过细胞体积的变化与迁移相联系。我们通过膜片钳实验结合原子力显微镜获得的高分辨率三维图像推断，钾通道高活性期与细胞收缩同时出现。通过用特定的钾通道阻滞剂局部灌流细胞体（后部）或片状伪足（细胞前部），我们揭示了MDCK - F细胞中钾通道活性的极性分布。钾通道在MDCK - F细胞的后部优先活跃。我们讨论了局部钾通道活性如何与其他与迁移相关的现象（如“尾部收缩”或不对称细胞 - 基质相互作用）协同作用，可能导致支持迁移的细胞体积局部变化。最后，我们定义了迁移上皮细胞的细胞极化。正常上皮细胞是“垂直”极化的，而转化细胞是“水平”极化的，即在运动平面内。这样一种独特的观点可能有助于更好地理解从正常分化的上皮细胞向致瘤性迁移细胞的转变。
