Uncoupling of K⁺ and Cl⁻ transport across the cell membrane in the process of regulatory volume decrease
2012
Yang, Linjie | Zhu, Linyan | Xu, Yue | Zhang, Haifeng | Ye, Wencai | Mao, Jianwen | Chen, Lixin | Wang, Liwei
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 pHₒ inhibited the volume-activated K⁺ outflow and RVD, but not the Cl⁻ outflow, while inhibition of H⁺ efflux or increase of pHₒ buffer 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.
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