Linked Life Data

20472984

Source:http://linkedlifedata.com/resource/pubmed/id/20472984

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-5-17
pubmed:abstractText
Tamoxifen inhibits transmembrane currents of the Kir2.x inward rectifier potassium channels by interfering with the interaction of the channels with membrane phosphatidylinositol 4,5-bisphosphate (PIP(2)). We tested the hypothesis that Kir channels with low affinity for PIP(2), like the adenosine triphosphate (ATP)-sensitive K(+) channel (K(ATP)) and acetylcholine (ACh)-activated K(+) channel (K(ACh)), have at least the same sensitivity to tamoxifen as Kir2.3. We investigated the effects of tamoxifen (0.1 - 10 microM) on Kir6.2/SUR2A (K(ATP)) and Kir3.1/3.4 (K(ACh)) channels expressed in HEK-293 cells and ATP-sensitive K(+) current (I(KATP)) and ACh-activated K(+) current (I(KACh)) in feline atrial myocytes. The onset of tamoxifen inhibition of both I(KATP) and I(KACh) was slow (T(1/2) approximately 3.5 min) and concentration-dependent but voltage-independent. The time course and degree of inhibition was independent of external or internal drug application. Tamoxifen interacts with the pore forming subunit, Kir6.2, rather than with the SUR subunit. The inhibitory potency of tamoxifen on the Kir6.2/SUR2A channel was decreased by the mutation (C166S) on Kir6.2 and in the continuous presence of PIP(2). In atrial myocytes, the mechanism and potency of the effects of tamoxifen on K(ATP) and K(ACh) channels were comparable to those in HEK-293 cells. These data suggest that, similar to its effects on Kir2.x currents, tamoxifen inhibits K(ATP) and K(ACh) currents by interfering with the interaction between the channel and PIP(2).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1347-8648
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
113
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
66-75
pubmed:dateRevised
2011-6-20
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Tamoxifen inhibits cardiac ATP-sensitive and acetylcholine-activated K+ currents in part by interfering with phosphatidylinositol 4,5-bisphosphate-channel interaction.
pubmed:affiliation
Unidad de Investigación Carlos Méndez del Centro Universitario de Investigaciones Biomédicas de la Universidad de Colima, México.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't