Open AccessIdentification and Characterization of Calcium Sparks in Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells
Author(s) -
Guang Qin Zhang,
Heming Wei,
Jun Lü,
Philip Wong,
Winston Shim
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0055266
Subject(s) - ryanodine receptor , induced pluripotent stem cell , endoplasmic reticulum , myocyte , calcium , extracellular , chemistry , calcium signaling , biophysics , voltage dependent calcium channel , calcium in biology , microbiology and biotechnology , biology , embryonic stem cell , biochemistry , organic chemistry , gene
Ca 2+ 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 Ca 2+ 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 Ca 2+ sparks in hiPSC-CMs were recorded with Ca 2+ 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 Ca 2+ spark were analogous to that of adult CMs. Inhibition of L-type Ca 2+ 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) Ca 2+ content. In contrast, high extracellular Ca 2+ and ryanodine increased the frequency, full width at half maximum (FWHM) and full duration at half maximum (FDHM) of spontaneous Ca 2+ sparks. Conclusions For the first time , spontaneous Ca 2+ sparks were detected in hiPSC-CMs. The Ca 2+ sparks are predominately triggered by L-type Ca 2+ channels mediated Ca 2+ influx, which is comparable to sparks detected in adult ventricular myocytes in which cardiac E-C coupling was governed by a Ca 2+ -induced Ca 2+ release (CICR) mechanism. However, focal repetitive sparks originated from the same intracellular organelle could reflect an immature status of the hiPSC-CMs.