Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-1-16
pubmed:abstractText
In heart, pore-forming Kv4 alpha channel subunits underlie the K(+) transient outward current (I(to)). Expression of Kv4 is greater in left ventricular epicardial (EPI) than in endocardial (ENDO) cells, resulting in larger I(to) in EPI than in ENDO cells. In adult ventricular myocytes, the transcription factor NFATc3 suppresses Kv4 expression. NFATc3 activity is higher in ENDO than in EPI cells and this has been proposed to contribute to heterogeneous Kv4 expression across the left ventricular free wall. Here, we tested the hypothesis that regional activation of NFATc3 signaling dissipates the gradient of I(to) density across the mouse left ventricle during chronic activation of beta adrenergic signaling. [Ca(2+)](i), calcineurin, and NFAT activity were larger in ENDO than in EPI myocytes. Infusion of the beta adrenergic receptor agonist isoproterenol increased [Ca(2+)](i), calcineurin, and NFAT activity in EPI, but not in ENDO myocytes, leading to equalization of these parameters in EPI and ENDO cells. This was accompanied by dissipation of the transmural gradient in Kv4.2 expression and I(to) density. Unlike wild type, ENDO or EPI myocytes from beta1 adrenergic receptor-null and NFATc3-null mice did not undergo changes in I(to) density during isoproterenol infusion. Collectively, these data suggest that calcineurin and NFATc3 signaling contributes to the loss of heterogeneous Kv4 expression, and hence I(to) density, in the mouse left ventricle during chronic beta adrenergic stimulation.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-10228181, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-10710358, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-10884375, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-11158275, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-11351020, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-11369778, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-11443045, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-11747815, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-11805844, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-11807805, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-11834482, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-11909823, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-12181147, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-12356880, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-12600876, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-14615291, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-14615493, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-15087419, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-15194740, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-15375008, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-15840485, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-160753, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-16239150, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-16423856, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-16614306, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-17350036, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-17387610, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-17537202, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-17557924, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-17578347, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-18323524, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-18451341, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-18723449, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-7929194, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-8275526, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-8635208, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-8693001, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-8831489, http://linkedlifedata.com/resource/pubmed/commentcorrection/19027024-9734479
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1095-8584
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
249-56
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
NFATc3-dependent loss of I(to) gradient across the left ventricular wall during chronic beta adrenergic stimulation.
pubmed:affiliation
Department of Physiology and Biophysics, University of Washington, Box 357290, Seattle, WA 98195, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural