Source:http://linkedlifedata.com/resource/pubmed/id/11078449
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
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| pubmed:dateCreated |
2000-11-15
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| pubmed:abstractText |
The factors that influence functional coupling between the sulfonylurea receptor (SUR1) and Kir6.2 subunits of ATP-sensitive K+ (K+(ATP)) channels were studied in rat pancreatic beta-cells using patch clamp and microfluorometric techniques. Tolbutamide at 10 micromol/l inhibited K+(ATP) channels in association with occurrence of action currents, but further exposure of beta-cells to the drug for 30 min or longer resulted in reappearance of K+(ATP) channel events. Half-maximal inhibition concentration (IC50) for tolbutamide was 1.5 microl/mol in 2.8 mmol/l glucose, and it was increased to 13.3 micromol/l when the cellular metabolism was inhibited by 0.5 mmol/l 2,4-dinitrophenol (DNP) for 5 min. Tolbutamide at 10 micromol/l induced an increase in cytosolic Ca2+ concentration ([Ca2+]i), and its amplitude was markedly reduced following exposure to 0.5 mmol/l DNP or long-term (30 min) exposure to 10 micromol/l tolbutamide. This tolbutamide insensitivity, as assessed by the [Ca2+]i response, was not observed when the external Ca2+ was omitted during the long-term exposure to tolbutamide. In cell-attached membrane patches, the tolbutamide insensitivity was also produced by treatment of cells with 150 micromol/l diazoxide and 25 mmol/l KCl in the presence, but not absence, of 2 mmol/l Ca2+ in the external solution. When the cytoplasmic face of inside-out membrane patches was treated with higher Ca2+ concentrations (2 micromol/l), both ADP-evoked activation and tolbutamide-induced inhibition of K+ ATP channels were attenuated with retaining ATP-induced inhibition, indicating the modification of K+(ATP) channels. The Ca2+-induced channel modification was prevented partially by phosphatidylinositol 4,5-bisphosphate (PIP2) and completely by ATP and PIP2 together, but not by ATP alone. Treatment of the channel with cytochalasin D, a disrupter of F-actin, evoked channel modification similar to that induced by Ca2+. The modification was prevented completely by phalloidin, a stabilizer of F-actin. In conclusion, long-term exposure to tolbutamide or metabolic inhibition causes modification of K+ ATP channels via mechanisms involving Ca2+-dependent reaction. The modification, which may reflect functional disconnection between SUR1 and Kir6.2, is prevented by ATP and PIP2, which may act cooperatively to stabilize membrane cytoskeletons (F-actin structures).
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2,4-Dinitrophenol,
http://linkedlifedata.com/resource/pubmed/chemical/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Diphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochalasin D,
http://linkedlifedata.com/resource/pubmed/chemical/Diazoxide,
http://linkedlifedata.com/resource/pubmed/chemical/Phalloidine,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 4,5-Diphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Chloride,
http://linkedlifedata.com/resource/pubmed/chemical/Tolbutamide
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0012-1797
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
49
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1830-9
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:11078449-2,4-Dinitrophenol,
pubmed-meshheading:11078449-Actins,
pubmed-meshheading:11078449-Adenosine Diphosphate,
pubmed-meshheading:11078449-Adenosine Triphosphate,
pubmed-meshheading:11078449-Animals,
pubmed-meshheading:11078449-Calcium,
pubmed-meshheading:11078449-Cytochalasin D,
pubmed-meshheading:11078449-Cytosol,
pubmed-meshheading:11078449-Diazoxide,
pubmed-meshheading:11078449-Electric Conductivity,
pubmed-meshheading:11078449-Islets of Langerhans,
pubmed-meshheading:11078449-Patch-Clamp Techniques,
pubmed-meshheading:11078449-Phalloidine,
pubmed-meshheading:11078449-Phosphatidylinositol 4,5-Diphosphate,
pubmed-meshheading:11078449-Potassium Channels,
pubmed-meshheading:11078449-Potassium Chloride,
pubmed-meshheading:11078449-Rats,
pubmed-meshheading:11078449-Rats, Wistar,
pubmed-meshheading:11078449-Tolbutamide
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| pubmed:year |
2000
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| pubmed:articleTitle |
PIP2 and ATP cooperatively prevent cytosolic Ca2+-induced modification of ATP-sensitive K+ channels in rat pancreatic beta-cells.
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| pubmed:affiliation |
First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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