Linked Life Data

9336346

Source:http://linkedlifedata.com/resource/pubmed/id/9336346

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-11-3
pubmed:abstractText
Levosimendan, a new Ca++-sensitizing and positive inotropic agent, was reported to act as a coronary vasodilator and protect ischemic myocardium. To elucidate the mechanisms of these actions, the possible electrophysiological effects of levosimendan on isolated rat ventricular cells were examined by the patch-clamp technique with whole-cell and single-channel recordings. Levosimendan (3 and 10 microM) markedly shortened action potential duration and activated an outward current at potentials positive to -70 mV. The increased current was abolished by glibenclamide, a blocker of the ATP-sensitive K+ (K[ATP]) current. Stimulation of K[ATP] current was dose dependent, with an EC50 value of 4.7 microM; a maximal effect occurred at 30 microM. The L-type Ca++ current was not affected by levosimendan (0.2-10 microM). In single-channel current recording in open cell-attached patches, K[ATP] channels, which had been inhibited by 0.3 mM ATP, were activated by levosimendan. However, levosimendan did not stimulate the K[ATP] channels that exhibited high spontaneous activity in ATP-free solution. Levosimendan also could not stimulate K[ATP] channels that had rundown in ATP-free solution. However, levosimendan could stimulate rundown K[ATP] channels that were reactivated by nucleotide diphosphates. K[ATP] channels inhibited by 0.5 mM AMP-PNP, a nonhydrolyzable ATP analog, were not stimulated by levosimendan; however, the channels were stimulated by levosimendan in the presence of 30 to 50 microM ADP. Levosimendan stimulates cardiac K[ATP] channels that are suppressed by intracellular ATP. It appears that levosimendan acts synergistically with nucleotide diphosphates. These properties of levosimendan may help protect ischemic myocardium because activation of K[ATP] channels by levosimendan would likely occur in ischemic regions in which intracellular ADP concentration is increased and intracellular ATP concentration is decreased.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
375-83
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
The novel calcium sensitizer levosimendan activates the ATP-sensitive K+ channel in rat ventricular cells.
pubmed:affiliation
Department of Molecular and Cellular Physiology, College of Medicine, University of Cincinnati, Ohio 45267-0576, USA. yokoshh@ucbeh.san.uc.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't