Linked Life Data

18024550

Source:http://linkedlifedata.com/resource/pubmed/id/18024550

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-2-12
pubmed:abstractText
Sphingosine-1-phosphate (S1P) induces a transient bradycardia in mammalian hearts through activation of an inwardly rectifying K(+) current (I(K(ACh))) in the atrium that shortens action potential duration (APD) in the atrium. We have investigated probable mechanisms and receptor-subtype specificity for S1P-induced negative inotropy in isolated adult mouse ventricular myocytes. Activation of S1P receptors by S1P (100 nM) reduced cell shortening by approximately 25% (vs. untreated controls) in field-stimulated myocytes. S1P(1) was shown to be involved by using the S1P(1)-selective agonist SEW2871 on myocytes isolated from S1P(3)-null mice. However, in these myocytes, S1P(3) can modulate a somewhat similar negative inotropy, as judged by the effects of the S1P(1) antagonist VPC23019. Since S1P(1) activates G(i) exclusively, whereas S1P(3) activates both G(i) and G(q), these results strongly implicate the involvement of mainly G(i). Additional experiments using the I(K(ACh)) blocker tertiapin demonstrated that I(K(ACh)) can contribute to the negative inotropy following S1P activation of S1P(1) (perhaps through G(ibetagamma) subunits). Mathematical modeling of the effects of S1P on APD in the mouse ventricle suggests that shortening of APD (e.g., as induced by I(K(ACh))) can reduce L-type calcium current and thus can decrease the intracellular Ca(2+) concentration ([Ca(2+)](i)) transient. Both effects can contribute to the observed negative inotropic effects of S1P. In summary, these findings suggest that the negative inotropy observed in S1P-treated adult mouse ventricular myocytes may consist of two distinctive components: 1) one pathway that acts via G(i) to reduce L-type calcium channel current, blunt calcium-induced calcium release, and decrease [Ca(2+)](i); and 2) a second pathway that acts via G(i) to activate I(K(ACh)) and reduce APD. This decrease in APD is expected to decrease Ca(2+) influx and reduce [Ca(2+)](i) and myocyte contractility.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0363-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
294
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H736-49
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18024550-Action Potentials, pubmed-meshheading:18024550-Animals, pubmed-meshheading:18024550-Calcium Channels, L-Type, pubmed-meshheading:18024550-Depression, Chemical, pubmed-meshheading:18024550-GTP-Binding Protein alpha Subunits, Gi-Go, pubmed-meshheading:18024550-Heart Ventricles, pubmed-meshheading:18024550-Lysophospholipids, pubmed-meshheading:18024550-Mice, pubmed-meshheading:18024550-Mice, Inbred C57BL, pubmed-meshheading:18024550-Models, Statistical, pubmed-meshheading:18024550-Myocardial Contraction, pubmed-meshheading:18024550-Myocytes, Cardiac, pubmed-meshheading:18024550-Potassium Channels, Inwardly Rectifying, pubmed-meshheading:18024550-Receptors, G-Protein-Coupled, pubmed-meshheading:18024550-Receptors, Lysosphingolipid, pubmed-meshheading:18024550-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:18024550-Signal Transduction, pubmed-meshheading:18024550-Sphingosine
pubmed:year
2008
pubmed:articleTitle
Mechanisms of the negative inotropic effects of sphingosine-1-phosphate on adult mouse ventricular myocytes.
pubmed:affiliation
Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't