Uncoupling of K+ and Cl- transport across the cell membrane in the process of regulatory volume decrease.
Uncoupling of K+ and Cl- transport across the cell membrane in the process of regulatory volume decrease.
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DOI：
10.1016/j.bcp.2012.05.006
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发表时间：
2012-08
影响因子：
5.8
通讯作者：
L. Yang;Linyan Zhu;Yue Xu;Haifeng Zhang;W. Ye;Jianwen Mao;Lixin Chen;Liwei Wang
中科院分区：
文献类型：
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作者：
L. Yang;Linyan Zhu;Yue Xu;Haifeng Zhang;W. Ye;Jianwen Mao;Lixin Chen;Liwei Wang
在调节性体积减少(RVD)过程中，K+和Cl2+−流是紧密耦合的。然而，利用自参比微电极，我们证明了鼻咽癌CNE-2Z细胞中K+和Cl-−的转运主要通过通道解偶联，瞬时的K+外流被提前激活，而持续的Cl-−外流被激活。低渗刺激降低了细胞内pH(Phi)，并激活了依赖于质子泵的H+外流，导致细胞外pH(Pho)下降。而抑制H+外流或增加pHO缓冲能力则促进K+外流和−外流。结果提示，由于K+和Cl−通道对邻苯二甲酸二苯酯的敏感性不同，RVD时K+通道和Cl−通道活动的时间动态不同。H+外流可能在细胞体积调节中发挥重要作用，并可能成为鼻咽癌的治疗靶点。
It is accepted that K+and Cl−flows are coupled tightly in regulatory volume decrease (RVD). However, using self referencing microelectrodes, we proved that K+and Cl−transport mainly by channels in RVD was uncoupled in nasopharyngeal carcinoma CNE-2Z cells, with the transient K+efflux activated earlier and sustained Cl−efflux activated later. Hypotonic challenges decreased intracellular pH (pHi), and activated a proton pump-dependent H+efflux, resulting in a decline of extracellular pH (pHo). Modest decreases of pHoinhibited the volume-activated K+outflow and RVD, but not the Cl−outflow, while inhibition of H+efflux or increase of pHobuffer ability promoted K+efflux and RVD. The results suggest that the temporal dynamics of K+channel activities is different from that of Cl−channels in RVD, due to differential sensitivity of K+and Cl−channels to pHo. H+efflux may play important roles in cell volume regulation, and may be a therapeutic target for human nasopharyngeal carcinoma.