K+ channel block-induced mammalian neuroblastoma cell swelling:: a possible mechanism to influence proliferation
K+ channel block-induced mammalian neuroblastoma cell swelling:: a possible mechanism to influence proliferation
复制标题
DOI：
10.1111/j.1469-7793.1998.093bz.x
复制
发表时间：
1998-07-01
影响因子：
5.5
通讯作者：
Dubois, JM
中科院分区：
文献类型：
--
作者：
Rouzaire-Dubois, B;Dubois, JM
1. 多项研究表明 K+ 通道活性是细胞进展至有丝分裂 G1 期的关键决定因素。我们之前提出 K+ 通道通过调节细胞体积来控制细胞周期调节蛋白的活性。为了验证这一假设，我们用库尔特计数器在不同的实验条件下测量了神经母细胞瘤×神经胶质瘤杂交细胞NG108-15的体积和增殖率。2． K+ 通道阻滞剂 TEA (1-10 nM)、4-氨基吡啶 (0.2-2 mM) 和 Cs+ (2.5-10 mM) 增加了细胞体积并降低了细胞增殖率。当细胞体积增加25%时，增殖被完全抑制。3．含有 NaCl 的培养基渗透压增加 40%，导致细胞体积增加 25%，细胞增殖率降低 82%。甘露醇培养基渗透压增加40%，细胞体积增加9%，细胞增殖率下降60%。4． Cl-通道阻断剂NPPB（5-硝基-2-(3-苯基丙氨基)苯甲酸；50μM）诱导细胞体积增加12%，细胞增殖率降低77%。5． H2O 使培养基渗透压降低 24%，导致细胞体积减少 21%，细胞增殖率增加 32%。6．在全细胞膜片钳条件下，抗生素（青霉素加链霉素）降低了电压依赖性 K+ 电流。培养基中省略抗生素导致细胞体积减少10%，细胞增殖率增加32%。7．这些结果表明控制细胞增殖的机制受到决定细胞体积的因素的强烈影响。这可以考虑 K+ 通道有丝分裂和参与细胞体积调节的其他离子途径的作用。
1. A variety of studies hare suggested that K+ channel activity is a key determinant for cell progression through the G1 phase of mitosis. We have previously proposed that K+ channels control the activity of cell cycle-regulating proteins via regulation of cell volume. In order to test this hypothesis, we measured, with a Coulter counter and under different experimental conditions, the volume and rate of proliferation of neuroblastoma x glioma hybrid NG108-15 cells.2. The K+ channel blockers TEA (1-10 nM), 4-aminopyridine (0.2-2 mM) and Cs+ (2.5-10 mM) increased the cell volume and decreased the rate of cell proliferation. Proliferation was fully inhibited when cell volume was increased by 25 %.3. A 40 % increase in the culture medium osmolarity With NaCl induced a 25 % increase in cell volume and an 82 % decrease in the rate of cell proliferation. A 40 % increase in the culture medium osmolarity with mannitol induced a 9 % increase in cell volume and a 60 % decrease in the rate of cell proliferation.4. The Cl- channel blocker NPPB (5-nitro-2-(3-phenylpropylamino) benzoic acid; 50 mu M) induced a 12 % increase in cell volume and a 77 % decrease in the rate of cell proliferation.5. A 24 % reduction in the culture medium osmolarity with H2O induced a 21 % decrease in cell volume and a 32 % increase in the rate of cell proliferation.6. Under whole-cell patch-clamp conditions, antibiotics (penicillin plus streptomycin) decreased the voltage-dependent K+ current. Omission of antibiotics from the culture medium induced a 10 % decrease in the cell volume and a 32 % increase in the rate of cell proliferation.7. These results suggest that the mechanisms controlling cell proliferation are strongly influenced by the factors which deter mine cell volume. This could take into account the role in mitogenesis of K+ channels and of other ionic pathways involved in cell volume regulation.