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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
30
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pubmed:dateCreated |
1996-9-3
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pubmed:abstractText |
These studies of a model liver cell line evaluate the mechanisms responsible for regulated release of K+ ions during metabolic stress. Metabolic inhibition of HTC hepatoma cells by exposure to 2, 4-dinitrophenol (50 microM) and 2-deoxy-D-glucose (10 mM) stimulated outward currents carried by K+ of 974 +/- 75 pA at 0 mV (n = 20, p < 0.001). Currents were inhibited by chelation of intracellular Ca2+ or exposure to apamin (50 nM), an inhibitor of SKCa channels. In cell-attached recordings from intact cells, removal of metabolic substrates (25/28 cells) or exposure to metabolic inhibitors (32/40 cells) opened K+-selective channels with a conductance of 6.5 +/- 0. 2 pS. Channels had an open probability of 0.31 +/- 0.08 and opened in bursts averaging 3.55 +/- 0.27 ms in duration (n = 6). Metabolic stress was associated with rapid translocation of the alpha isoform of protein kinase C (PKCalpha) from cytosol to membrane; and down-regulation of PKCalpha by phorbol esters or exposure to the PKC inhibitor chelerythrine (10 microM) each inhibited currents. Moreover, intracellular perfusion with purified PKCalpha activated currents in a Ca2+- and concentration-dependent manner. These findings indicate that metabolic stress leads to opening of apamin-sensitive SKCa channels in hepatoma cells through a Ca2+- and PKC-dependent mechanism and suggest that PKCalpha may be selectively involved in the response. This mechanism functionally couples the metabolic state of cells to membrane K+ permeability and represents a potential target for modification of liver injury associated with ischemia and preservation.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2,4-Dinitrophenol,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyglucose,
http://linkedlifedata.com/resource/pubmed/chemical/Dinitrophenols,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/calcium-dependent protein kinase
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
26
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pubmed:volume |
271
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
18107-13
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:8663472-2,4-Dinitrophenol,
pubmed-meshheading:8663472-Adenosine Triphosphate,
pubmed-meshheading:8663472-Amino Acid Sequence,
pubmed-meshheading:8663472-Animals,
pubmed-meshheading:8663472-Biological Transport,
pubmed-meshheading:8663472-Calcium,
pubmed-meshheading:8663472-Deoxyglucose,
pubmed-meshheading:8663472-Dinitrophenols,
pubmed-meshheading:8663472-Electric Conductivity,
pubmed-meshheading:8663472-Electric Impedance,
pubmed-meshheading:8663472-Enzyme Inhibitors,
pubmed-meshheading:8663472-Ion Channel Gating,
pubmed-meshheading:8663472-Isoenzymes,
pubmed-meshheading:8663472-Liver,
pubmed-meshheading:8663472-Molecular Sequence Data,
pubmed-meshheading:8663472-Potassium,
pubmed-meshheading:8663472-Potassium Channels,
pubmed-meshheading:8663472-Protein Kinase C,
pubmed-meshheading:8663472-Protein Kinase C-alpha,
pubmed-meshheading:8663472-Protein Kinases,
pubmed-meshheading:8663472-Rats,
pubmed-meshheading:8663472-Tumor Cells, Cultured
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pubmed:year |
1996
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pubmed:articleTitle |
Metabolic stress opens K+ channels in hepatoma cells through a Ca2+- and protein kinase calpha-dependent mechanism.
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pubmed:affiliation |
Department of Medicine, Duke University Medical Center Durham, North Carolina 27710, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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