Identification and characterization of calcium sparks in cardiomyocytes derived from human induced pluripotent stem cells.
INTRODUCTION: Ca2+ spark constitutes the elementary units of cardiac excitation-contraction (E-C) coupling in mature cardiomyocytes. Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes are known to have electrophysiological properties similar to mature adult cardiomyocytes. However, i...
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doaj-1359d14240454932b91f9ae479a3012a2020-11-25T01:57:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5526610.1371/journal.pone.0055266Identification and characterization of calcium sparks in cardiomyocytes derived from human induced pluripotent stem cells.Guang Qin ZhangHeming WeiJun LuPhilip WongWinston ShimINTRODUCTION: Ca2+ spark constitutes the elementary units of cardiac excitation-contraction (E-C) coupling in mature cardiomyocytes. Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes are known to have electrophysiological properties similar to mature adult cardiomyocytes. However, it is unclear if they share similar calcium handling property. We hypothesized that Ca2+ sparks in human induced pluripotent stem cell (hiPSCs)-derived cardiomyocytes (hiPSC-CMs) may display unique structural and functional properties than mature adult cardiomyocytes. METHODS AND RESULTS: Ca2+ sparks in hiPSC-CMs were recorded with Ca2+ imaging assay with confocal laser scanning microscopy. Those sparks were stochastic with a tendency of repetitive occurrence at the same site. Nevertheless, the spatial-temporal properties of Ca2+ spark were analogous to that of adult CMs. Inhibition of L-type Ca2+ channels by nifedipine caused a 61% reduction in calcium spark frequency without affecting amplitude of those sparks and magnitude of caffeine releasable sarcoplasmic reticulum (SR) Ca2+ content. In contrast, high extracellular Ca2+ and ryanodine increased the frequency, full width at half maximum (FWHM) and full duration at half maximum (FDHM) of spontaneous Ca2+ sparks. CONCLUSIONS: For the first time, spontaneous Ca2+ sparks were detected in hiPSC-CMs. The Ca2+ sparks are predominately triggered by L-type Ca2+ channels mediated Ca2+ influx, which is comparable to sparks detected in adult ventricular myocytes in which cardiac E-C coupling was governed by a Ca2+-induced Ca2+ release (CICR) mechanism. However, focal repetitive sparks originated from the same intracellular organelle could reflect an immature status of the hiPSC-CMs.http://europepmc.org/articles/PMC3567046?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Guang Qin Zhang Heming Wei Jun Lu Philip Wong Winston Shim |
spellingShingle |
Guang Qin Zhang Heming Wei Jun Lu Philip Wong Winston Shim Identification and characterization of calcium sparks in cardiomyocytes derived from human induced pluripotent stem cells. PLoS ONE |
author_facet |
Guang Qin Zhang Heming Wei Jun Lu Philip Wong Winston Shim |
author_sort |
Guang Qin Zhang |
title |
Identification and characterization of calcium sparks in cardiomyocytes derived from human induced pluripotent stem cells. |
title_short |
Identification and characterization of calcium sparks in cardiomyocytes derived from human induced pluripotent stem cells. |
title_full |
Identification and characterization of calcium sparks in cardiomyocytes derived from human induced pluripotent stem cells. |
title_fullStr |
Identification and characterization of calcium sparks in cardiomyocytes derived from human induced pluripotent stem cells. |
title_full_unstemmed |
Identification and characterization of calcium sparks in cardiomyocytes derived from human induced pluripotent stem cells. |
title_sort |
identification and characterization of calcium sparks in cardiomyocytes derived from human induced pluripotent stem cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
INTRODUCTION: Ca2+ spark constitutes the elementary units of cardiac excitation-contraction (E-C) coupling in mature cardiomyocytes. Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes are known to have electrophysiological properties similar to mature adult cardiomyocytes. However, it is unclear if they share similar calcium handling property. We hypothesized that Ca2+ sparks in human induced pluripotent stem cell (hiPSCs)-derived cardiomyocytes (hiPSC-CMs) may display unique structural and functional properties than mature adult cardiomyocytes. METHODS AND RESULTS: Ca2+ sparks in hiPSC-CMs were recorded with Ca2+ imaging assay with confocal laser scanning microscopy. Those sparks were stochastic with a tendency of repetitive occurrence at the same site. Nevertheless, the spatial-temporal properties of Ca2+ spark were analogous to that of adult CMs. Inhibition of L-type Ca2+ channels by nifedipine caused a 61% reduction in calcium spark frequency without affecting amplitude of those sparks and magnitude of caffeine releasable sarcoplasmic reticulum (SR) Ca2+ content. In contrast, high extracellular Ca2+ and ryanodine increased the frequency, full width at half maximum (FWHM) and full duration at half maximum (FDHM) of spontaneous Ca2+ sparks. CONCLUSIONS: For the first time, spontaneous Ca2+ sparks were detected in hiPSC-CMs. The Ca2+ sparks are predominately triggered by L-type Ca2+ channels mediated Ca2+ influx, which is comparable to sparks detected in adult ventricular myocytes in which cardiac E-C coupling was governed by a Ca2+-induced Ca2+ release (CICR) mechanism. However, focal repetitive sparks originated from the same intracellular organelle could reflect an immature status of the hiPSC-CMs. |
url |
http://europepmc.org/articles/PMC3567046?pdf=render |
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