Abstract
Ca2p spark constitutes the elementary units of cardiac excitation-contraction (E-C) coupling. To understand the mechanisms of E-C coupling in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), we measured spontaneous Ca2p sparks in hiPSC-CMs and investigated their
Highlights
Ca2+ spark constitutes the elementary units of cardiac excitation-contraction (E-C) coupling in mature cardiomyocytes
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
The pluripotent status of Human induced pluripotent stem cell (hiPSC) was confirmed by their expression of pluripotent markers and by their pluripotent differentiation potential including embryoid body (EB) formation and cardiac differentiation in vitro and teratoma formation in vivo. hiPSCs were maintained on mouse embryonic fibroblasts (MEF) feeder in human embryonic stem cells (hESCs) medium (80% Knockout Dulbecco’s Modified Eagle Medium or DMEM, 20% Serum replacement, 1% non-essential amino acid, 1 mM Lglutamine, 0.1 mM beta-mercaptoethanol and 4 ng/mL bFGF)
Summary
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. It is unclear if they share similar calcium handling property. RyR Ca2+ release channel is tightly linked to the gating of L-type Ca2+ channel and plays a key role in the intracellular Ca2+-handling in cardiac myocytes [4]. Such property of Ca2+ sparks may reflect the organizational maturity of RyRs in the cardiomyocytes [5]
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