title: Uncoupling of K+ and Cl- transport across the cell membrane in the process of regulatory volume decrease.
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.
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China. eyanglinjie@163.com
authors.forename: Linjie
authors.initials: L
authors.lastname: Yang
authors.forename: Linyan
authors.initials: L
authors.lastname: Zhu
authors.forename: Yue
authors.initials: Y
authors.lastname: Xu
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.forename: Wencai
authors.initials: W
authors.lastname: Ye
authors.forename: Jianwen
authors.initials: J
authors.lastname: Mao
authors.forename: Lixin
authors.initials: L
authors.lastname: Chen
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
mesh_terms: D002277:Carcinoma; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011188:Potassium