Contractile Properties of Early Human Embryonic Stem Cell-Derived Cardiomyocytes: Beta-Adrenergic Stimulation Induces Positive Chronotropy and Lusitropy but Not Inotropy

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) provide the unique opportunity to study the very early development of the human heart. The aim of this study was to investigate the effect of calcium and beta-adrenergic stimulation on the contractile properties of early hESC-CMs. Beating clusters containing hESC-CMs were co-cultured in vitro with noncontractile slices of neonatal murine ventricles. After 5–7 days, when beating clusters had integrated morphologically into the damaged tissue, isometric force measurements were performed during spontaneous beating as well as during electrical field stimulation. Spontaneous beating stopped when extracellular calcium ([Ca2+]ec) was removed or after administration of the Ca2+ channel blocker nifedipine. During field stimulation at a constant rate, the developed force increased with incremental concentrations of [Ca2+]ec. During spontaneous beating, rising [Ca2+]ec increased beating rate and developed force up to a [Ca2+]ec of 2.5 mM. When [Ca2+]ec was ...