Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-2-22
pubmed:abstractText
Membrane Cl(-) channels play an important role in cell volume homeostasis and regulation of volume-sensitive cell transport and metabolism. Heterologous expression of ClC-2 channel cDNA leads to the appearance of swelling-activated Cl(-) currents, consistent with a role in cell volume regulation. Since channel properties in heterologous models are potentially modified by cellular background, we evaluated whether endogenous ClC-2 proteins are functionally important in cell volume regulation. As shown by whole cell patch clamp techniques in rat HTC hepatoma cells, cell volume increases stimulated inwardly rectifying Cl(-) currents when non-ClC-2 currents were blocked by DIDS (100 microM). A cDNA closely homologous with rat brain ClC-2 was isolated from HTC cells; identical sequence was demonstrated for ClC-2 cDNAs in primary rat hepatocytes and cholangiocytes. ClC-2 mRNA and membrane protein expression was demonstrated by in situ hybridization, immunocytochemistry, and Western blot. Intracellular delivery of antibodies to an essential regulatory domain of ClC-2 decreased ClC-2-dependent currents expressed in HEK-293 cells. In HTC cells, the same antibodies prevented activation of endogenous Cl(-) currents by cell volume increases or exposure to the purinergic receptor agonist ATP and delayed HTC cell volume recovery from swelling. These studies provide further evidence that mammalian ClC-2 channel proteins are functional and suggest that in HTC cells they contribute to physiological changes in membrane Cl(-) permeability and cell volume homeostasis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0193-1857
pubmed:author
pubmed:issnType
Print
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G344-53
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11171616-4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid, pubmed-meshheading:11171616-Animals, pubmed-meshheading:11171616-Antibodies, pubmed-meshheading:11171616-Carcinoma, Hepatocellular, pubmed-meshheading:11171616-Cell Line, pubmed-meshheading:11171616-Cell Membrane, pubmed-meshheading:11171616-Cell Size, pubmed-meshheading:11171616-Chloride Channels, pubmed-meshheading:11171616-Chlorides, pubmed-meshheading:11171616-DNA, Complementary, pubmed-meshheading:11171616-Epithelial Cells, pubmed-meshheading:11171616-Hepatocytes, pubmed-meshheading:11171616-Homeostasis, pubmed-meshheading:11171616-Humans, pubmed-meshheading:11171616-Microinjections, pubmed-meshheading:11171616-Patch-Clamp Techniques, pubmed-meshheading:11171616-Rats, pubmed-meshheading:11171616-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11171616-Transfection
pubmed:year
2001
pubmed:articleTitle
ClC-2 chloride channels contribute to HTC cell volume homeostasis.
pubmed:affiliation
Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't