Document Detail


Chloride accumulation drives volume dynamics underlying cell proliferation and migration.
MedLine Citation:
PMID:  19036868     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
During brain development, progenitor cells migrate over long distances through narrow and tortuous extracellular spaces posing significant demands on the cell's ability to alter cell volume. This phenotype is recapitulated in primary brain tumors. We demonstrate here that volume changes occurring spontaneously in these cells are mediated by the flux of Cl- along with obligated water across the cell membrane. To do so, glioma cells accumulate Cl- to approximately 100 mM, a concentration threefold greater than predicted by the Nernst equation. Shunting this gradient through the sustained opening of exogenously expressed GABA-gated Cl- channels caused a 33% decrease in cell volume and impaired the ability of cells to migrate in a spatially constrained environment. Further, dividing cells condense their cytoplasm prior to mitosis, a phenomenon which is associated with the release of intracellular Cl- as indicated by a 40-mM decrease in [Cl-]i. These findings provide a new framework for considering the role of intracellular Cl- in glioma cells. Here, Cl- serves as an important osmotically active regulator of cell volume being the energetic driving force for volume changes required by immature cells in cell migration and proliferation. This mechanism that was studied in CNS malignancies may be shared with other immature cells in the brain as well.
Authors:
Christa W Habela; Nola Jean Ernest; Amanda F Swindall; Harald Sontheimer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-11-26
Journal Detail:
Title:  Journal of neurophysiology     Volume:  101     ISSN:  0022-3077     ISO Abbreviation:  J. Neurophysiol.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-06     Completed Date:  2009-03-26     Revised Date:  2013-06-04    
Medline Journal Info:
Nlm Unique ID:  0375404     Medline TA:  J Neurophysiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  750-7     Citation Subset:  IM    
Affiliation:
Department of Neurobiology, Center for Glial Biology in Medicine, University of Alabama, 1719 6th Ave. S., CIRC 425, Birmingham, AL 35294, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetates / pharmacology
Analysis of Variance
Bumetanide / pharmacology
Cell Line, Tumor
Cell Movement / drug effects,  physiology*
Cell Proliferation* / drug effects
Cell Size* / drug effects
Chlorides / metabolism*
Electric Stimulation / methods
GABA Antagonists / pharmacology
Glioblastoma
Green Fluorescent Proteins / genetics
Humans
Imaging, Three-Dimensional / methods
Indenes / pharmacology
Membrane Potentials / drug effects,  physiology
Patch-Clamp Techniques / methods
Picrotoxin / pharmacology
Sodium Potassium Chloride Symporter Inhibitors / pharmacology
Transfection
gamma-Aminobutyric Acid / pharmacology
Grant Support
ID/Acronym/Agency:
P50-CA-97247/CA/NCI NIH HHS; R01-NS-313234/NS/NINDS NIH HHS; R01-NS-36692/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Acetates; 0/Chlorides; 0/GABA Antagonists; 0/Indenes; 0/Sodium Potassium Chloride Symporter Inhibitors; 106105-17-3/((2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy)acetic acid; 124-87-8/Picrotoxin; 147336-22-9/Green Fluorescent Proteins; 28395-03-1/Bumetanide; 56-12-2/gamma-Aminobutyric Acid
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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