Uncoupling of K+ and Cl- transport across the cell membrane in the process of regulatory volume decrease

It is accepted that le and Cl- flows are coupled tightly in regulatory volume decrease (RVD). However, using self referencing microelectrodes, we proved that le 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 le outflow and RVD, but not the Cl- outflow, while inhibition of H+ efflux or increase of pH, 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. (C) 2012 Published by Elsevier Inc.