Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-4-16
pubmed:abstractText
Regulatory subunit KCNE3 (E3) interacts with KCNQ1 (Q1) in epithelia, regulating its activation kinetics and augmenting current density. Since E3 is expressed weakly in the heart, we hypothesized that ectopic expression of E3 in cardiac myocytes might abbreviate action potential duration (APD) by interacting with Q1 and augmenting the delayed rectifier current (I(K)). Thus, we transiently coexpressed E3 with Q1 and KCNE1 (E1) in Chinese hamster ovary cells and found that E3 coexpression increased outward current at potentials by > or = -80 mV and accelerated activation. We then examined the changes in cardiac electrophysiology following injection of adenovirus-expressed E3 into the left ventricular cavity of guinea pigs. After 72 hours, the corrected QT interval of the electrocardiogram was reduced by approximately 10%. APD was reduced by >3-fold in E3-transduced cells relative to controls, while E-4031-insensitive I(K) and activation kinetics were significantly augmented. Based on quantitative modeling of a transmural cardiac segment, we demonstrate that the degree of QT interval abbreviation observed results from electrotonic interactions in the face of limited transduction efficiency and that heterogeneous transduction of E3 may actually potentiate arrhythmias. Provided that fairly homogeneous ectopic ventricular expression of regulatory subunits can be achieved, this approach may be useful in enhancing repolarization and in treating long QT syndrome.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-10024355, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-10082479, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-10219239, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-10393695, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-10646604, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-10653833, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-10709243, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-10746995, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-10775148, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-10898519, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-10933926, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-10973849, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-11104781, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-11185581, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-11207363, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-11239413, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-11320260, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-11426298, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-11557234, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-11701509, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-2170562, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-7881134, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-8431990, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-8900283, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-8927497, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-9032314, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-9354802, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-9560262, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-9798514, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-9799214, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-9799215, http://linkedlifedata.com/resource/pubmed/commentcorrection/11956246-9852064
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9738
pubmed:author
pubmed:issnType
Print
pubmed:volume
109
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1083-90
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed-meshheading:11956246-Animals, pubmed-meshheading:11956246-Animals, Genetically Modified, pubmed-meshheading:11956246-CHO Cells, pubmed-meshheading:11956246-Cricetinae, pubmed-meshheading:11956246-Female, pubmed-meshheading:11956246-Gene Expression, pubmed-meshheading:11956246-Gene Therapy, pubmed-meshheading:11956246-Guinea Pigs, pubmed-meshheading:11956246-Heart Conduction System, pubmed-meshheading:11956246-Humans, pubmed-meshheading:11956246-KCNQ Potassium Channels, pubmed-meshheading:11956246-KCNQ1 Potassium Channel, pubmed-meshheading:11956246-Long QT Syndrome, pubmed-meshheading:11956246-Models, Cardiovascular, pubmed-meshheading:11956246-Potassium Channels, pubmed-meshheading:11956246-Potassium Channels, Voltage-Gated, pubmed-meshheading:11956246-Transfection, pubmed-meshheading:11956246-Ventricular Function
pubmed:year
2002
pubmed:articleTitle
Ectopic expression of KCNE3 accelerates cardiac repolarization and abbreviates the QT interval.
pubmed:affiliation
Department of Medicine, Institute of Molecular Cardiobiology, Johns Hopkins University, 720 Rutland Avenue, Baltimore, MD 21205, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't