Linked Life Data

9395071

Source:http://linkedlifedata.com/resource/pubmed/id/9395071

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-1-7
pubmed:abstractText
Rectification of HERG is due to a rapid inactivation process that has been labeled C-type inactivation and is believed to be due to closure of the external mouth of the pore. We examined the effects of mutation of extracellular residues that remove C-type inactivation on binding of the intracellularly acting methanesulfonanilide drug E-4031. Removal of inactivation through mutation reduced drug affinity by more than an order of magnitude. Elevation of [K+]o in the wild-type channel reduces channel affinity for E-4031. Elevation of [K+]o also interferes with the extracellular pore mouth closure associated with C-type inactivation through a 'foot in the door' mechanism. We examined the possibility that [K+]o elevation reduces drug binding through inhibition of C-type inactivation by comparing drug block in the wild-type and inactivation-removed mutant channels. Elevation of [K+]o decreased affinity in both channel constructs by a roughly equal amount. These results suggest that [K+]o alters drug binding affinity independently of its effects on C-type inactivation. They further suggest that inhibition of pore mouth closure by elevated [K+]o does not have same effect on drug affinity as mutations removing C-type inactivation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0014-5793
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
417
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
43-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Modulation of HERG affinity for E-4031 by [K+]o and C-type inactivation.
pubmed:affiliation
Department of Medicine, Duke University Medical Center, Durham, NC 27708-0281, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't