Document Detail

Lithium inhibits cell volume regulation by acting on chloride channels and modifies ultrastructures of the cell membrane in nasopharyngeal carcinoma cells.
MedLine Citation:
PMID:  20522412     Owner:  NLM     Status:  MEDLINE    
Lithium salts have been used as a class of mood stabilizing agents to treat bipolar disorders for over a century. Although lithium is known to affect cell proliferation, apoptosis and migration, the underlying mechanisms have not been well-explored. Emerging evidence indicates that cell volume regulation and volume-activated chloride channels are involved in cell proliferation, apoptosis and migration. To understand the mechanism of lithium's actions, we investigated the effect of lithium chloride on cell volume regulation and volume-activated chloride channels in the nasopharyngeal carcinoma cell line CNE-2Z. Our results show that lithium chloride attenuates regulatory volume decrease induced by 47% hypotonic challenges in a concentration-dependent manner with an IC(50) of 756 microM. Using the patch clamp techniques, we further show that lithium chloride concentration-dependently (IC(50)=440 microM) inhibits the volume-activated chloride current as well as the background chloride current. Furthermore, using a nanoscale atomic force microscope, we show that lithium chloride prevents the hypotonic challenge-induced changes in the ultrastructures of the cell membrane. These changes include an increase in the number and the size of the small holes, which are observed in the surface of the cell membrane under isotonic conditions. The lithium chloride-induced inhibition in cell volume regulation, in volume-activated chloride current and in the ultrastructures of the cell membrane may contribute to its effects on cell proliferation, apoptosis and migration.
Zhiquan Bai; Haifeng Zhang; Linyan Zhu; Wanhong Zuo; Jianghong Ye; Jianqiang Feng; Liwei Wang; Lixin Chen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-27
Journal Detail:
Title:  European journal of pharmacology     Volume:  641     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-07-15     Completed Date:  2011-01-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  88-95     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier B.V. All rights reserved.
Department of Physiology, Medical College, Jinan University, Guangzhou, China.
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MeSH Terms
Apoptosis / drug effects
Carcinoma / metabolism,  pathology
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
Cell Size / drug effects*
Chloride Channels / antagonists & inhibitors,  metabolism*,  physiology
Chlorides / metabolism,  pharmacology
Dose-Response Relationship, Drug
Erythrocyte Membrane / metabolism,  ultrastructure
Inhibitory Concentration 50
Lithium Compounds / therapeutic use*
Microscopy, Atomic Force
Nasopharyngeal Neoplasms / metabolism*,  pathology*
Patch-Clamp Techniques
Reg. No./Substance:
0/Chloride Channels; 0/Chlorides; 0/Lithium Compounds

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