Lang Florian, Föller Michael, Lang Karl, Lang Philipp, Ritter Markus, Vereninov Alexey, Szabo Ildiko, Huber Stephan M, Gulbins Erich
Department of Physiology, University of Tübingen, Germany.
Methods Enzymol. 2007;428:209-25. doi: 10.1016/S0076-6879(07)28011-5.
Alterations of cell volume are key events during both cell proliferation and apoptotic cell death. Cell proliferation eventually requires an increase of cell volume, and apoptosis is typically paralleled by cell shrinkage. Alterations of cell volume require the participation of ion transport across the cell membrane, including appropriate activity of Cl(-) and K(+) channels. Cl(-) channels modify cytosolic Cl(-) activity and mediate osmolyte flux, and thus influence cell volume. Most Cl(-) channels allow exit of HCO(3)(-), leading to cytosolic acidification, which in turn inhibits cell proliferation and favors apoptosis. K(+) exit through K(+) channels decreases cytosolic K(+) concentration, which may sensitize the cell for apoptotic cell death. K(+) channel activity further maintains the cell membrane potential, a critical determinant of Ca(2+) entry through Ca(2+) channels. Ca(2+) may, in addition, enter through Ca(2+)-permeable cation channels, which, in some cells, are activated by hyperosmotic shock. Increases of cytosolic Ca(2+) activity may trigger both mechanisms required for cell proliferation and mechanisms, leading to apoptosis. Thereby cell proliferation and apoptosis depend on magnitude and temporal organization of Ca(2+) entry, as well as activity of other signaling pathways. Accordingly, the same ion channels may participate in the stimulation of both cell proliferation and apoptosis. Specific ion channel blockers may thus abrogate both cellular mechanisms, depending on cell type and condition.
细胞体积的改变是细胞增殖和凋亡性细胞死亡过程中的关键事件。细胞增殖最终需要细胞体积增大，而凋亡通常伴随着细胞收缩。细胞体积的改变需要跨细胞膜的离子转运参与，包括Cl(-)和K(+)通道的适当活性。Cl(-)通道调节胞质Cl(-)活性并介导渗透溶质通量，从而影响细胞体积。大多数Cl(-)通道允许HCO(3)(-)流出，导致胞质酸化，进而抑制细胞增殖并促进凋亡。通过K(+)通道的K(+)外流降低胞质K(+)浓度，这可能使细胞对凋亡性细胞死亡敏感。K(+)通道活性进一步维持细胞膜电位，这是Ca(2+)通过Ca(2+)通道进入的关键决定因素。此外，Ca(2+)可能通过Ca(2+)通透阳离子通道进入，在某些细胞中，这些通道由高渗休克激活。胞质Ca(2+)活性的增加可能触发细胞增殖所需的机制以及导致凋亡的机制。因此，细胞增殖和凋亡取决于Ca(2+)进入的幅度和时间组织，以及其他信号通路的活性。相应地，相同的离子通道可能参与细胞增殖和凋亡的刺激。因此，特定的离子通道阻滞剂可能消除这两种细胞机制，这取决于细胞类型和条件。
