Linked Life Data

9843803

Source:http://linkedlifedata.com/resource/pubmed/id/9843803

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6 Pt 2
pubmed:dateCreated
1999-2-1
pubmed:abstractText
FK-506 increases the cytosolic Ca2+ concentration transient in rat ventricular myocytes by prolonging the action potential through inhibition of the K+ currents Ito and IK [J. Physiol. (Lond.) 501: 509-516, 1997]. Physiological and biochemical techniques were used in parallel to examine the electrophysiological mechanisms and the role of calcineurin inhibition in these effects. FK-506 prolonged the recovery of Ito from inactivation. Thus Ito inhibition was frequency dependent, with no decrease at 0.2 Hz (recorded at +50 mV from -70 mV) but a 40% decrease at 2.0 Hz. In contrast, inhibition of IK ( approximately 60%) was time and voltage independent. At 25 microM, FK-506 (by 65%) and cyclosporin A (by 57%) inhibited calcineurin activity in myocyte extracts. However, only FK-506 increased the cytosolic Ca2+ concentration transient in field-stimulated myocytes. Furthermore, FK-506 was still active on K+ currents when cells were dialyzed with 10 mM EGTA. These results demonstrate that calcineurin inhibition is not responsible for the functional effects of FK-506 in heart and suggest that IK and Ito are modulated by FK-506-binding proteins or directly by FK-506.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0002-9513
pubmed:author
pubmed:issnType
Print
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H2041-52
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Independent inhibition of calcineurin and K+ currents by the immunosuppressant FK-506 in rat ventricle.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, Maryland 21201, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.