Source:http://linkedlifedata.com/resource/pubmed/id/18818435
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
2008-12-19
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pubmed:abstractText |
On the basis of previous findings suggesting that in human embryonic stem cell-derived cardiomyocytes (hESC-CM) the sarcoplasmic reticulum Ca(2+)-induced release of calcium machinery is either absent or immature, in the present study we tested the hypothesis that hESC-CM contain fully functional 1,4,5-inositol trisphosphate (1,4,5-IP(3))-operated intracellular Ca(2+) ([Ca(2+)](i)) stores that can be mobilized upon appropriate physiological stimuli. To test this hypothesis we investigated the effects of angiotensin-II (AT-II) and endothelin-1 (ET-1), which activate the 1,4,5-IP(3) pathway, on [Ca(2+)](i) transients and contractions in beating clusters of hESC-CM. Our major findings were that in paced hESC-CM both AT-II and ET-1 (10(-9) to 10(-7) M) increased the contraction amplitude and the maximal rates of contraction and relaxation. In addition, AT-II (10(-9) to 10(-7) M) increased the [Ca(2+)](i) transient amplitude. The involvement of 1,4,5-IP(3)-dependent intracellular Ca(2+) release in the inotropic effect of AT-II was supported by the findings that (a) hESC-CM express AT-II, ET-1, and 1,4,5-IP(3) receptors determined by immunofluorescence staining, and (b) the effects of AT-II were blocked by 2 microM 2-aminoethoxyphenyl borate (a 1,4,5-IP(3) receptor blocker) and U73122 (a phospholipase C blocker). In conclusion, these findings demonstrate for the first time that hESC-CM exhibit functional AT-II and ET-1 signaling pathways, as well as 1,4,5-IP(3)-operated releasable Ca(2+) stores.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1549-4918
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
26
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3130-8
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pubmed:meshHeading |
pubmed-meshheading:18818435-Angiotensin II,
pubmed-meshheading:18818435-Animals,
pubmed-meshheading:18818435-Calcium,
pubmed-meshheading:18818435-Cells, Cultured,
pubmed-meshheading:18818435-Embryonic Stem Cells,
pubmed-meshheading:18818435-Endothelin-1,
pubmed-meshheading:18818435-Enzyme Inhibitors,
pubmed-meshheading:18818435-Humans,
pubmed-meshheading:18818435-Inositol 1,4,5-Trisphosphate Receptors,
pubmed-meshheading:18818435-Mice,
pubmed-meshheading:18818435-Models, Biological,
pubmed-meshheading:18818435-Myocytes, Cardiac,
pubmed-meshheading:18818435-Receptors, Adrenergic, beta,
pubmed-meshheading:18818435-Signal Transduction
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pubmed:year |
2008
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pubmed:articleTitle |
1,4,5-Inositol trisphosphate-operated intracellular Ca(2+) stores and angiotensin-II/endothelin-1 signaling pathway are functional in human embryonic stem cell-derived cardiomyocytes.
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pubmed:affiliation |
Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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