Document Detail

Recovery from lactacidosis-induced glial cell swelling with the aid of exogenous anion channels.
MedLine Citation:
PMID:  12528180     Owner:  NLM     Status:  MEDLINE    
Hypotonic challenge induces transient swelling in glial cells, which is typically followed by a regulatory volume decrease (RVD). In contrast, lactic acidosis (lactacidosis) induces persistent cell swelling in astrocytes without an accompanying RVD. In the present study, we studied the mechanisms by which lactacidosis interferes with normal volume regulation in rat astrocytic glioma C6 cells. Following exposure of C6 cells to a hypotonic challenge, a current was detected that exhibited properties consistent with those of volume-sensitive outwardly rectifying (VSOR) anion channels. When exposed to in vitro conditions designed to simulate lactacidosis, C6 cells failed to respond to hypotonic stress with an RVD, and VSOR anion currents were not activated. When added to C6 cells, an anion channel-forming protein purified from Helicobacter pylori, VacA, was found to form anion-selective channels in the plasma membrane, and the activity of the VacA channel was not affected by lactacidosis (pH 6.2). Cells preincubated with VacA and then exposed to lactacidotic conditions underwent transient swelling followed by RVD. In contrast, application of a cation ionophore, gramicidin, failed to inhibit lactacidosis-induced persistent cell swelling. From these results, we conclude that inhibition of a volume-sensitive anion channel contributes to persistent swelling induced by lactacidosis in glial cells. Introduction of anion channel activity into glial cells might provide a novel approach for treating cerebral edema, which is associated with lactacidosis in cerebral ischemia or head injury.
Takashi Nabekura; Shigeru Morishima; Timothy L Cover; Shin-Ichiro Mori; Hiroshi Kannan; Shizuo Komune; Yasunobu Okada
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Glia     Volume:  41     ISSN:  0894-1491     ISO Abbreviation:  Glia     Publication Date:  2003 Feb 
Date Detail:
Created Date:  2003-01-15     Completed Date:  2003-04-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8806785     Medline TA:  Glia     Country:  United States    
Other Details:
Languages:  eng     Pagination:  247-59     Citation Subset:  IM    
Copyright Information:
Copyright 2003 Wiley-Liss, Inc.
Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
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MeSH Terms
Acidosis, Lactic / metabolism*
Anions / metabolism
Bacterial Proteins / genetics,  metabolism*
Cell Membrane / metabolism
Hypotonic Solutions / pharmacology
Membrane Potentials / physiology
Neuroglia / metabolism*,  pathology
Patch-Clamp Techniques
Tumor Cells, Cultured
Water-Electrolyte Balance / physiology
Reg. No./Substance:
0/Anions; 0/Bacterial Proteins; 0/Hypotonic Solutions; 0/VacA protein, Helicobacter pylori

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