rdf:type |
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lifeskim:mentions |
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pubmed:issue |
Pt 1
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pubmed:dateCreated |
2001-11-16
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pubmed:abstractText |
1. Large-conductance Ca(2+)- and voltage-activated potassium (BK) channels are important regulators of cellular excitability. Here, we present a patch-clamp electrophysiological analysis of splice-variant-specific regulation by the synthetic glucocorticoid dexamethasone (DEX) of BK channels consisting of cloned STREX or ZERO alpha-subunit variants expressed in human embryonic kidney (HEK 293) cells. 2. STREX channels in isolated membrane patches were inhibited by protein kinase A (PKA) and this was blocked on pre-treatment of intact cells with DEX (100 nM) for 2 h. 3. The effect of DEX required the synthesis of new mRNA and protein. Furthermore, it required protein phosphatase 2A (PP2A)-like activity intimately associated with the channels, as it was blocked by 10 nM okadaic acid but not by the specific protein phosphatase-1 inhibitor peptide PPI-2. 4. ZERO variant channels that lack the STREX insert were activated by PKA but were not influenced by DEX. ZERO channels containing a mutant STREX domain (S4(STREX)A) were also activated by PKA. Importantly, DEX blocked PKA activation of S4(STREX)A channels in a PP2A-dependent manner. 5. Taken together, the STREX domain is crucial for glucocorticoid regulation of BK channels through a PP2A-type enzyme. Moreover, glucocorticoids appear to induce a generic set of proteins in different types of cells, the actions of which depend on the expression of cell-specific targets.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-10066921,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-10200423,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-10517674,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-10696570,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-10766916,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-10871603,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-11309619,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-11331373,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-1332850,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-1497890,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-1646298,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-1710783,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-1791837,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-2781292,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-2867473,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-7515569,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-7588309,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-7597086,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-7687074,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-7769088,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-7790924,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-7987297,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-7993625,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-8621576,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-8858210,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-9115223,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-9545224,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-9593688,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11711561-9614096
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoids,
http://linkedlifedata.com/resource/pubmed/chemical/Large-Conductance...,
http://linkedlifedata.com/resource/pubmed/chemical/Large-Conductance...,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Phosphatase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Phosphatase 2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucocorticoid
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-3751
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
537
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
57-68
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:11711561-Alternative Splicing,
pubmed-meshheading:11711561-Animals,
pubmed-meshheading:11711561-Cell Line,
pubmed-meshheading:11711561-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:11711561-Dexamethasone,
pubmed-meshheading:11711561-Glucocorticoids,
pubmed-meshheading:11711561-Humans,
pubmed-meshheading:11711561-Large-Conductance Calcium-Activated Potassium Channel...,
pubmed-meshheading:11711561-Large-Conductance Calcium-Activated Potassium Channels,
pubmed-meshheading:11711561-Mice,
pubmed-meshheading:11711561-Phosphoprotein Phosphatases,
pubmed-meshheading:11711561-Potassium Channel Blockers,
pubmed-meshheading:11711561-Potassium Channels,
pubmed-meshheading:11711561-Potassium Channels, Calcium-Activated,
pubmed-meshheading:11711561-Protein Biosynthesis,
pubmed-meshheading:11711561-Protein Isoforms,
pubmed-meshheading:11711561-Protein Phosphatase 1,
pubmed-meshheading:11711561-Protein Phosphatase 2,
pubmed-meshheading:11711561-Protein Structure, Tertiary,
pubmed-meshheading:11711561-RNA, Messenger,
pubmed-meshheading:11711561-Receptors, Glucocorticoid
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pubmed:year |
2001
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pubmed:articleTitle |
Alternative splicing determines sensitivity of murine calcium-activated potassium channels to glucocorticoids.
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pubmed:affiliation |
Membrane Biology Group and MRC "Membrane and Adapter Protein" COOP, Section of Biomedical Sciences, University of Edinburgh Medical School, Hugh Robson Building, Edinburgh EH8 9XD, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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