Cell cycle-dependent activity of the volume- and Ca2+-activated anion currents in Ehrlich Lettre Ascites cells
Cell cycle-dependent activity of the volume- and Ca2+-activated anion currents in Ehrlich Lettre Ascites cells
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DOI：
10.1002/jcp.20918
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发表时间：
2007-03-01
影响因子：
5.6
通讯作者：
Hoffmann, Else K.
中科院分区：
文献类型：
--
作者：
Klausen, Thomas Kjaer;Bergdahl, Andreas;Hoffmann, Else K.
最近的证据表明，容量调节阴离子电流（VRAC）和其他阴离子电流在控制或调节细胞周期的进展，然而，在这个过程中的阴离子通道的确切参与还不清楚。在此，在细胞周期进程中监测埃利希腹水癌（ELA）细胞中的Cl-电流。VRAC），（ii）在细胞内游离Ca 2+浓度增加后（即，Ca 2+激活的Cl-电流，CaCO 3），和（iii）在稳态等渗条件下。与G 0期相比，GI期最大肿胀激活VRAC电流降低，S期早期增加。等渗稳态电流，这似乎是主要的VRAC，也减少了在G1，并再次增加，在早期S期，在G 0的水平相似。相反，最大CaCC电流（移液管中500 nM游离Ca 2+）从G 0到GI没有改变，但在早期S期降低。一种新型的高亲和力阴离子通道抑制剂，酸性二芳基脲NS 3728，抑制VRAC和CaCC，衰减ELA细胞生长，表明细胞周期进程和细胞周期依赖性变化的能力之间的可能的机制联系导电氯离子运输。这表明，在ELA细胞，进入S期需要增加VRAC活性和/或增加的潜力，调节体积减少（RVD），并在同一时间减少CaCC幅度。
Recent evidence implicates the volume-regulated anion current (VRAC) and other anion currents in control or modulation of cell cycle progression; however, the precise involvement of anion channels in this process is unclear. Here, Cl- currents in Ehrlich Lettre Ascites (ELA) cells were monitored during cell cycle progression, Under three conditions: (i) after osmotic swelling (i.e., VRAC), (ii) after an increase in the free intracellular Ca2+ concentration (i.e., the Ca2+-activated Cl- current, CaCC), and (iii) under steady-state isotonic conditions. The maximal swelling-activated VRAC Current decreased in GI and increased in early S phase, compared to that in G0. The isotonic steady-state current, which seems to be predominantly VRAC, also decreased in G1, and increased again in early S phase, to a level similar to that in G0. In contrast, the maximal CaCC current (500 nM free Ca2+ in the pipette), was unaltered from G0 to GI, but decreased in early S phase. A novel high-affinity anion channel inhibitor, the acidic di-aryl-urea NS3728, which inhibited both VRAC and CaCC, attenuated ELA cell growth, suggesting a possible mechanistic link between cell cycle progression and cell cycle-dependent changes in the capacity for conductive Cl- transport. It is suggested that in ELA cells, entrance into the S phase requires an increase in VRAC activity and/or an increased potential for regulatory volume decrease (RVD), and at the same time a decrease in CaCC magnitude.