pubmed-article:10087343 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:10087343 | lifeskim:mentions | umls-concept:C0031715 | lld:lifeskim |
pubmed-article:10087343 | lifeskim:mentions | umls-concept:C0037492 | lld:lifeskim |
pubmed-article:10087343 | lifeskim:mentions | umls-concept:C1419853 | lld:lifeskim |
pubmed-article:10087343 | pubmed:dateCreated | 1999-6-29 | lld:pubmed |
pubmed-article:10087343 | pubmed:abstractText | 1. Protein kinase A (PKA) modulation of tetrodotoxin-resistant (TTX-r) voltage-gated sodium channels may underly the hyperalgesic responses of mammalian sensory neurones. We have therefore examined PKA phosphorylation of the cloned alpha-subunit of the rat sensory neurone-specific TTX-r channel SNS. Phosphorylation of SNS was compared with that of a mutant channel, SNS(SA), in which all five PKA consensus sites (RXXS) within the intracellular I-II loop had been eliminated by site-directed mutagenesis (serine to alanine). 2. In vitro PKA phosphorylation and tryptic peptide mapping of SNS and mutant SNS(SA) I-II loops expressed as glutathione-S-transferase (GST) fusion proteins confirmed that the five mutated serines were the major PKA substrates within the SNS I-II loop. 3. SNS and SNS(SA) channels were transiently expressed in COS-7 cells and their electrophysiological properties compared. In wild-type SNS channels, forskolin and 8-bromo cAMP produced effects consistent with PKA phosphorylation. Mutant SNS(SA) currents, however, were not significantly affected by either agent. Thus, elimination of the I-II loop PKA consensus sites caused a marked reduction in PKA modulation of wild-type channels. 4. Under control conditions, the voltage dependence of activation of SNS(SA) current was shifted to depolarized potentials compared with SNS. This was associated with a slowing of SNS(SA) current inactivation at hyperpolarized potentials and suggested a tonic PKA phosphorylation of wild-type channels under basal conditions.5. We conclude that the major substrates involved in functional PKA modulation of the SNS channel are located within the intracellular I-II loop. | lld:pubmed |
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pubmed-article:10087343 | pubmed:language | eng | lld:pubmed |
pubmed-article:10087343 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:10087343 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:10087343 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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pubmed-article:10087343 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:10087343 | pubmed:month | Apr | lld:pubmed |
pubmed-article:10087343 | pubmed:issn | 0022-3751 | lld:pubmed |
pubmed-article:10087343 | pubmed:author | pubmed-author:DolphinA CAC | lld:pubmed |
pubmed-article:10087343 | pubmed:author | pubmed-author:FitzgeraldE... | lld:pubmed |
pubmed-article:10087343 | pubmed:author | pubmed-author:MossS JSJ | lld:pubmed |
pubmed-article:10087343 | pubmed:author | pubmed-author:WoodJ NJN | lld:pubmed |
pubmed-article:10087343 | pubmed:author | pubmed-author:OkuseKK | lld:pubmed |
pubmed-article:10087343 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:10087343 | pubmed:day | 15 | lld:pubmed |
pubmed-article:10087343 | pubmed:volume | 516 ( Pt 2) | lld:pubmed |
pubmed-article:10087343 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:10087343 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:10087343 | pubmed:pagination | 433-46 | lld:pubmed |
pubmed-article:10087343 | pubmed:dateRevised | 2010-8-25 | lld:pubmed |
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pubmed-article:10087343 | pubmed:year | 1999 | lld:pubmed |
pubmed-article:10087343 | pubmed:articleTitle | cAMP-dependent phosphorylation of the tetrodotoxin-resistant voltage-dependent sodium channel SNS. | lld:pubmed |
pubmed-article:10087343 | pubmed:affiliation | Department of Pharmacology, University College London, London WC1E 6BT, UK. | lld:pubmed |
pubmed-article:10087343 | pubmed:publicationType | Journal Article | lld:pubmed |