Identification and characterization of calcium sparks in cardiomyocytes derived from human induced pluripotent stem cells.

Identification and characterization of calcium sparks in cardiomyocytes derived from human induced pluripotent stem cells.

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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 Knob 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 Tripping Collars 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.