Linked Life Data

14656703

Source:http://linkedlifedata.com/resource/pubmed/id/14656703

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-3-15
pubmed:abstractText
Reducing the ATP sensitivity of the sarcolemmal ATP-sensitive K(+) (K(ATP)) channel is predicted to lead to active channels in normal metabolic conditions and hence cause shortened ventricular action potentials and reduced myocardial inotropy. We generated transgenic (TG) mice that express an ATP-insensitive K(ATP) channel mutant [Kir6.2(deltaN2-30,K185Q)] under transcriptional control of the alpha-myosin heavy chain promoter. Strikingly, myocyte contraction amplitude was increased in TG myocytes (15.68 +/- 1.15% vs. 10.96 +/- 1.49%), even though K(ATP) channels in TG myocytes are very insensitive to inhibitory ATP. Under normal metabolic conditions, steady-state outward K(+) currents measured under whole cell voltage clamp were elevated in TG myocytes, consistent with threshold K(ATP) activation, but neither the monophasic action potential measured in isolated hearts nor transmembrane action potential measured in right ventricular muscle preparations were shortened at physiological pacing cycles. Taken together, these results suggest that there is a compensatory remodeling of excitation-contraction coupling in TG myocytes. Whereas there were no obvious differences in other K(+) conductances, peak L-type Ca(2+) current (I(Ca)) density (-16.42 +/- 2.37 pA/pF) in the TG was increased compared with the wild type (-8.43 +/- 1.01 pA/pF). Isoproterenol approximately doubled both I(Ca) and contraction amplitude in wild-type myocytes but failed to induce a significant increase in TG myocytes. Baseline and isoproterenol-stimulated cAMP concentrations were not different in wild-type and TG hearts, suggesting that the enhancement of I(Ca) in the latter does not result from elevated cAMP. Collectively, the data demonstrate that a compensatory increase in I(Ca) counteracts a mild activation of ATP-insensitive K(ATP) channels to maintain the action potential duration and elevate the inotropic state of TG hearts.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0363-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H1361-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Remodeling of excitation-contraction coupling in transgenic mice expressing ATP-insensitive sarcolemmal KATP channels.
pubmed:affiliation
Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.