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  • Title: Uncoupling of K+ and Cl- transport across the cell membrane in the process of regulatory volume decrease.
    Author: Yang L, Zhu L, Xu Y, Zhang H, Ye W, Mao J, Chen L, Wang L.
    Journal: Biochem Pharmacol; 2012 Aug 01; 84(3):292-302. PubMed ID: 22617318.
    Abstract:
    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 (pH(i)), and activated a proton pump-dependent H(+) efflux, resulting in a decline of extracellular pH (pH(o)). Modest decreases of pH(o) inhibited the volume-activated K(+) outflow and RVD, but not the Cl(-) outflow, while inhibition of H(+) efflux or increase of pH(o) 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 pH(o). H(+) efflux may play important roles in cell volume regulation, and may be a therapeutic target for human nasopharyngeal carcinoma.
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