| Local control of excitation-contraction coupling in human embryonic stem cell-derived cardiomyocytes. | |
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MedLine Citation:
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PMID: 19404384 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We investigated the mechanisms of excitation-contraction (EC) coupling in human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and fetal ventricular myocytes (hFVMs) using patch-clamp electrophysiology and confocal microscopy. We tested the hypothesis that Ca(2+) influx via voltage-gated L-type Ca(2+) channels activates Ca(2+) release from the sarcoplasmic reticulum (SR) via a local control mechanism in hESC-CMs and hFVMs. Field-stimulated, whole-cell [Ca(2+)](i) transients in hESC-CMs required Ca(2+) entry through L-type Ca(2+) channels, as evidenced by the elimination of such transients by either removal of extracellular Ca(2+) or treatment with diltiazem, an L-type channel inhibitor. Ca(2+) release from the SR also contributes to the [Ca(2+)](i) transient in these cells, as evidenced by studies with drugs interfering with either SR Ca(2+) release (i.e. ryanodine and caffeine) or reuptake (i.e. thapsigargin and cyclopiazonic acid). As in adult ventricular myocytes, membrane depolarization evoked large L-type Ca(2+) currents (I(Ca)) and corresponding whole-cell [Ca(2+)](i) transients in hESC-CMs and hFVMs, and the amplitude of both I(Ca) and the [Ca(2+)](i) transients were finely graded by the magnitude of the depolarization. hESC-CMs exhibit a decreasing EC coupling gain with depolarization to more positive test potentials, "tail" [Ca(2+)](i) transients upon repolarization from extremely positive test potentials, and co-localized ryanodine and sarcolemmal L-type Ca(2+) channels, all findings that are consistent with the local control hypothesis. Finally, we recorded Ca(2+) sparks in hESC-CMs and hFVMs. Collectively, these data support a model in which tight, local control of SR Ca(2+) release by the I(Ca) during EC coupling develops early in human cardiomyocytes. |
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Authors:
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Wei-Zhong Zhu; Luis F Santana; Michael A Laflamme |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-04-30 |
Journal Detail:
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Title: PloS one Volume: 4 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2009 |
Date Detail:
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Created Date: 2009-04-30 Completed Date: 2009-08-07 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
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Languages: eng Pagination: e5407 Citation Subset: IM |
Affiliation:
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Department of Pathology, University of Washington, Seattle, Washington, United States of America. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Calcium
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metabolism Calcium Channels, L-Type / metabolism* Cells, Cultured Electrophysiology Embryonic Stem Cells / cytology*, physiology Humans Membrane Potentials Myocardial Contraction* Myocytes, Cardiac / cytology, physiology* Sarcoplasmic Reticulum / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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HL064387/HL/NHLBI NIH HHS; HL080431/HL/NHLBI NIH HHS; HL085686/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Calcium Channels, L-Type; 7440-70-2/Calcium |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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