| pubmed-article:15136567 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15136567 | lifeskim:mentions | umls-concept:C0439799 | lld:lifeskim |
| pubmed-article:15136567 | lifeskim:mentions | umls-concept:C0243071 | lld:lifeskim |
| pubmed-article:15136567 | lifeskim:mentions | umls-concept:C0059503 | lld:lifeskim |
| pubmed-article:15136567 | pubmed:issue | 28 | lld:pubmed |
| pubmed-article:15136567 | pubmed:dateCreated | 2004-7-5 | lld:pubmed |
| pubmed-article:15136567 | pubmed:abstractText | In some A-type voltage-gated K channels, rapid inactivation is achieved through the binding of an N-terminal domain of the pore-forming alpha-subunit or an associated beta-subunit to a cytoplasmic acceptor located at or near the channel pore using the ball-and-chain machinery (1-5). This inactivation involving the N terminus is known as N-type inactivation. Here, we describe an erbstatin (Erb) analogue as a small molecule inhibitor of the N-type inactivation in channels of Kv1.4 and Kv1.1+Kvbeta1. We show that this inhibition of inactivation (designated as "disinactivation") is potent and selective for N-type inactivation in heterologous cells (Chinese hamster ovary and Xenopus oocytes) expressing these A-type channels. In Chinese hamster ovary cells, Erb increased the inactivation time constant of Kv1.4 from 86.5 +/- 9.5 to 150 +/- 10 ms (n = 6, p < 0.0 1). Similarly, Erb increased the inactivation time constant of Kv1.1+Kvbeta1 from 10 +/- 0.9 to 49.3 +/- 7 ms (n = 7, p < 0.01). The EC(50) for disinactivating Kv1.1+Kvbeta1 was 10.4 +/- 0.9 microm (n = 2-9). Erb had no effect upon another A-channel, Kv4.3, which does not utilize the ball-and-chain mechanism. The mechanism of Erb-induced disinactivation was also investigated. Neither cysteine oxidation nor tyrosine kinase inhibition was involved. The results demonstrate that Erb can be used as a base structure to identify potent, selective small molecule inhibitors of intracellular protein-protein interactions, and that these disinactivators may offer another therapeutic approach to the treatment of seizure disorders. | lld:pubmed |
| pubmed-article:15136567 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15136567 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15136567 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:15136567 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15136567 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15136567 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15136567 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15136567 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15136567 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15136567 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15136567 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15136567 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15136567 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15136567 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15136567 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15136567 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15136567 | pubmed:month | Jul | lld:pubmed |
| pubmed-article:15136567 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:15136567 | pubmed:author | pubmed-author:RhodesKenneth... | lld:pubmed |
| pubmed-article:15136567 | pubmed:author | pubmed-author:WangQiangQ | lld:pubmed |
| pubmed-article:15136567 | pubmed:author | pubmed-author:ArgentieriTho... | lld:pubmed |
| pubmed-article:15136567 | pubmed:author | pubmed-author:ZhangZhi-HaoZ... | lld:pubmed |
| pubmed-article:15136567 | pubmed:author | pubmed-author:ChildersWayne... | lld:pubmed |
| pubmed-article:15136567 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15136567 | pubmed:day | 9 | lld:pubmed |
| pubmed-article:15136567 | pubmed:volume | 279 | lld:pubmed |
| pubmed-article:15136567 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15136567 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15136567 | pubmed:pagination | 29226-30 | lld:pubmed |
| pubmed-article:15136567 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:meshHeading | pubmed-meshheading:15136567... | lld:pubmed |
| pubmed-article:15136567 | pubmed:year | 2004 | lld:pubmed |
| pubmed-article:15136567 | pubmed:articleTitle | Disinactivation of N-type inactivation of voltage-gated K channels by an erbstatin analogue. | lld:pubmed |
| pubmed-article:15136567 | pubmed:affiliation | Department of Women's Health and Bone, Wyeth Research, Collegeville, Pennsylvania 19426, USA. | lld:pubmed |
| pubmed-article:15136567 | pubmed:publicationType | Journal Article | lld:pubmed |
| entrez-gene:3736 | entrezgene:pubmed | pubmed-article:15136567 | lld:entrezgene |
| entrez-gene:3739 | entrezgene:pubmed | pubmed-article:15136567 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:15136567 | lld:entrezgene |
| http://linkedlifedata.com/r... | entrezgene:pubmed | pubmed-article:15136567 | lld:entrezgene |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:15136567 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:15136567 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:15136567 | lld:pubmed |
