Document Detail

Impaired activity of volume-sensitive anion channel during lactacidosis-induced swelling in neuronally differentiated NG108-15 cells.
MedLine Citation:
PMID:  12443974     Owner:  NLM     Status:  MEDLINE    
Acidosis coupled to lactate accumulation, called lactacidosis, occurs in cerebral ischemia or trauma and is known to cause persistent swelling in neuronal and glial cells. It is therefore possible that mechanisms of cell volume regulation are impaired during lactacidosis. Here we tested this possibility using neuronally differentiated NG108-15 cells. These cells responded to a hypotonic challenge with osmotic swelling followed by a regulatory volume decrease (RVD) under physiological pH conditions in the absence of lactate. Under normotonic conditions, sustained cell swelling without subsequent RVD was induced by exposure to lactate-containing solution with acidic pH (6.4 or 6.2), but not with physiological pH (7.4). Under whole-cell patch-clamp, osmotic swelling was found to activate outwardly rectifying Cl(-) currents in cells exposed to control hypotonic solution. A Cl(-) channel blocker, NPPB, inhibited both RVD and the swelling-activated Cl(-) current. RVD and the volume-sensitive Cl(-) current were also markedly inhibited by lactacidosis (pH 6.4 or 6.2), but neither by application of lactate with physiological pH (7.4) nor by acidification without lactate (pH 6.2). RT-PCR analysis showed mRNA expression of two isoforms of proton-coupled monocarboxylate transporters, MCT1 and MCT8, in differentiated NG108-15 cells. Thus, we conclude that persistence of neuronal cell swelling under lactacidosis is coupled to an impairment of the activity of the volume-sensitive Cl(-) channel and to dysfunction of RVD. It is also suggested that the volume-sensitive Cl(-) channel is inhibited by intracellular acidification induced by MCT-mediated proton influx under lactacidosis.
Shin-ichiro Mori; Shigeru Morishima; Mayumi Takasaki; Yasunobu Okada
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain research     Volume:  957     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-11-21     Completed Date:  2003-03-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1-11     Citation Subset:  IM    
Department of Cell Physiology, National Institute for Physiological Sciences, Myodaiji-cho, Okazaki 444-8585, Japan.
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MeSH Terms
Acidosis, Lactic / metabolism*
Cell Culture Techniques
Cell Line
Cell Size / drug effects
Chloride Channels / antagonists & inhibitors,  metabolism*
Edema / metabolism
Hypotonic Solutions
Ion Channels / drug effects,  metabolism
Monocarboxylic Acid Transporters / genetics,  metabolism*
Neurons / drug effects,  metabolism*
Nitrobenzoates / pharmacology
Patch-Clamp Techniques
Reverse Transcriptase Polymerase Chain Reaction
Symporters / metabolism
Reg. No./Substance:
0/Anions; 0/Chloride Channels; 0/Hypotonic Solutions; 0/Ion Channels; 0/Monocarboxylic Acid Transporters; 0/Nitrobenzoates; 0/Symporters; 0/monocarboxylate transport protein 1; 107254-86-4/5-nitro-2-(3-phenylpropylamino)benzoic acid

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

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