Cell swelling as an intermediate signal leading to activation of a Cl- channel in extracellular calcium-sensing of murine osteoclasts.
Cell swelling as an intermediate signal leading to activation of a Cl- channel in extracellular calcium-sensing of murine osteoclasts.
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细胞肿胀作为中间信号，导致小鼠破骨细胞细胞外钙感应中 Cl- 通道的激活。
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
M. Kuno
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作者：
K. Sakuta;H. Morihata;H. Mori;H. Sakai;M. Kuno
破骨细胞拥有细胞外 Ca2+ 感应机制来调节骨吸收活动。在小鼠破骨细胞中，细胞外 Ca2+ 浓度的升高激活了体积敏感的向外整流 Cl- (OR(Cl)) 通道。暴露于 40 mM Ca2+ 会激活 OR(Cl) 电流，并导致平面细胞面积增加。肌动蛋白去稳定剂（细胞松弛素 D）、主要细胞外渗透剂 (Na+) 的去除以及 Na+/Ca2+ 交换剂的阻断剂（2'4'-二氯苯甲酰胺盐酸盐）可抑制细胞外 Ca2+ 对 OR(Cl) 通道的肿胀和激活。电流密度与细胞面积增量呈正相关。使用共焦扫描显微镜在细胞外培养基中使用荧光染料 (BCECF) 进行三维分析，在完整（未夹紧的）细胞中证实了细胞外 Ca2+ 诱导的肿胀。这些结果表明，肿胀是破骨细胞细胞外 Ca2+ 感应的中间信号，从而导致 OR(Cl) 通道的激活。细胞体积可能是破骨细胞功能调节的第二信息。
Osteoclasts possess extracellular Ca2+-sensing machinery to regulate bone-resorbing activity. In murine osteoclasts, an elevation of the extracellular Ca2+ concentration activated a volume-sensitive outwardly rectifying Cl- (OR(Cl)) channel. Exposure to 40 mM Ca2+ activated the OR(Cl) current in association with an increase in the planar cell area. An actin-destabilizer (cytochalasin D), removal of a major extracellular osmolyte (Na+), and a blocker for the Na+/Ca2+ exchanger (2'4'-dichlorobenzamil hydrochloride) inhibited both swelling and activation of the OR(Cl) channel by extracellular Ca2+. There was a positive correlation between the current density and increment in the cell area. The extracellular Ca2+-induced swelling was confirmed in intact (unclamped) cells by three-dimensional analysis using confocal scanning microscopy with a fluorescent dye (BCECF) in the extracellular medium. These results suggest that swelling is an intermediate signal for extracellular Ca2+ sensing of osteoclasts, which leads to activation of the OR(Cl) channel. Cell volume may be a second-message in the regulation of osteoclast function.