Source:http://linkedlifedata.com/resource/pubmed/id/15605386
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2005-5-4
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pubmed:abstractText |
Coexpression of the serum and glucocorticoid inducible kinase 1 (SGK1) up-regulates Kv channel activity in Xenopus oocytes and human embryonic kidney cells. To investigate the physiological impact of SGK1 dependent Kv channel regulation, we recorded whole-cell currents in lung fibroblasts from SGK1 knockout mice (sgk1-/-) and wild-type littermates (sgk1+/+). Serum-grown mouse lung fibroblasts (MLF) from both genotypes exhibited voltage-gated outwardly rectifying K(+)-currents with time-dependent activation (tau(act) approximately 3 msec), slow inactivation (tau(inact) approximately 700 msec), use-dependent inactivation, and (partial) inhibition by K(+) channel blockers TEA, 4-AP, and margatoxin. In serum grown MLF peak Kv current density at +100 mV was significantly lower in sgk1-/- (14 +/- 2 pA/pF, n = 13) than in sgk1+/+ (31 +/- 4 pA/pF, n = 16). PCR amplification of different Kv1 and Kv3 subunits from mouse fibroblasts demonstrated the expression of Kv1.1-1.7, Kv3.1, and Kv3.3 mRNA in both sgk1+/+ and sgk1-/- cells. Upon serum deprivation Kv currents almost disappeared in sgk1+/+ (4 +/- 1 pA/pF, n = 11) but not in sgk1-/- (10 +/- 1 pA/pF, n = 6) MLF. Accordingly, following serum deprivation Kv current density was significantly lower in sgk1+/+ than in sgk1-/-. Stimulation of serum-depleted cells with dexamethasone (dex) (1 microM, 1 day), IGF-1 (6.7 microM, 4-6 h) or both, significantly activated Kv currents in sgk1+/+ but not in sgk1-/- MLF. In the presence of both, dex and IGF-1, the Kv current density was significantly larger in sgk1+/+ (27 +/- 3 pA/pF, n = 12) than in sgk1-/- (13 +/- 3 pA/pF, n = 10) cells. Similar to MLF, Kv currents were significantly higher in sgk1+/+ mouse tail fibroblasts (MTF). In sgk1+/+ but not sgk1-/- MTF the Kv currents were inhibited upon serum deprivation and reincreased after stimulation of serum deprived MTF with dex (1 microM, 1 day) and afterwards with IGF-1 (6.7 microM, 4-6 h). According to Fura-2-fluorescence capacitative Ca(2+) entry was lower in sgk1-/- MTF compared to sgk1+/+ MTF. Upon serum deprivation capacitative Ca(2+) entry decreased significantly in sgk1+/+ but not in sgk1-/- MTF. Stimulation of depleted cells with dex (1 microM, 1 day) and afterwards with IGF-1 (6.7 microM, 4-6 h) reincreased capacitative Ca(2+) entry in sgk1+/+ MTF, whereas in sgk1-/- cells it remained unchanged. In conclusion, lack of SGK1 does not abrogate Kv channel activity but abolishes regulation of those channels by serum, glucocorticoids and IGF-1, an effect influencing capacitative Ca(2+) entry.
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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/Blood Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoids,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels, Voltage-Gated,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Shaker Superfamily of Potassium...,
http://linkedlifedata.com/resource/pubmed/chemical/Shaw Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/serum-glucocorticoid regulated...
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9541
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pubmed:author |
pubmed-author:GrahammerFlorianF,
pubmed-author:HenkeGuidoG,
pubmed-author:KuhlDietmarD,
pubmed-author:LampertAngelikaA,
pubmed-author:LangFlorianF,
pubmed-author:LupescuAdrianA,
pubmed-author:MyssinaSvetlanaS,
pubmed-author:ShumilinaEkaterinaE,
pubmed-author:Strutz-SeebohmNathalieN,
pubmed-author:WulffPeerP
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pubmed:copyrightInfo |
(c) 2004 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:volume |
204
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
87-98
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:15605386-Animals,
pubmed-meshheading:15605386-Blood Proteins,
pubmed-meshheading:15605386-Calcium,
pubmed-meshheading:15605386-Cells, Cultured,
pubmed-meshheading:15605386-Fibroblasts,
pubmed-meshheading:15605386-Gene Expression Regulation,
pubmed-meshheading:15605386-Glucocorticoids,
pubmed-meshheading:15605386-Immediate-Early Proteins,
pubmed-meshheading:15605386-Lung,
pubmed-meshheading:15605386-Membrane Potentials,
pubmed-meshheading:15605386-Mice,
pubmed-meshheading:15605386-Mice, Knockout,
pubmed-meshheading:15605386-Nuclear Proteins,
pubmed-meshheading:15605386-Patch-Clamp Techniques,
pubmed-meshheading:15605386-Potassium Channels,
pubmed-meshheading:15605386-Potassium Channels, Voltage-Gated,
pubmed-meshheading:15605386-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15605386-RNA, Messenger,
pubmed-meshheading:15605386-Shaker Superfamily of Potassium Channels,
pubmed-meshheading:15605386-Shaw Potassium Channels,
pubmed-meshheading:15605386-Tail
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pubmed:year |
2005
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pubmed:articleTitle |
Deranged Kv channel regulation in fibroblasts from mice lacking the serum and glucocorticoid inducible kinase SGK1.
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pubmed:affiliation |
Department of Physiology, University of Tuebingen, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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