1–3 These beating EBs contain cardiac myocytes (CMs) based on the expression of cardiac-specific genes, cellular ultrastructure, and extracellular electrical activity. Recent studies have demonstrated that human embryonic stem (hES) cells in vitro can form embryoid bodies (EBs), some of which begin to spontaneously contract. Thus, hES provide a renewable source of distinct types of human cardiac myocytes for basic research, pharmacological testing, and potentially therapeutic applications. In conclusion, hES cells can differentiate into multiple types of CMs displaying functional properties characteristic of embryonic human cardiac muscle. Repolarization of the AP showed a significant role for I Kr based on E-4031 induced prolongation of AP duration as anticipated for human CMs. Complex functional properties typical of cardiac muscle were observed in the hES cell-derived CMs including rate adaptation of AP duration and provoked early and delayed afterdepolarizations. Repeated impalements of an individual beating outgrowth revealed a reproducible AP morphology recorded from different cells, suggesting that each outgrowth is composed of a predominant cell type. The APs were described as embryonic based on the relatively depolarized resting membrane potential and slow AP upstroke. Intracellular electrical recordings using sharp KCl microelectrodes in beating EB outgrowths revealed three distinct classes of APs: nodal-like, embryonic atrial-like, and embryonic ventricular-like. β-Adrenergic stimulation with 1.0 μmol/L isoproterenol resulted in a significant increase in contraction magnitude. Spontaneous and electrical field-stimulated contractions were measured with video edge-detection microscopy. This study characterizes the contractions and action potentials (APs) from beating EB outgrowths cultured for 40 to 95 days. Spontaneously contracting outgrowths from these EBs contain cardiomyocytes (CMs) however, the types of human CMs and their functional properties are unknown. Human embryonic stem (hES) cells can differentiate in vitro, forming embryoid bodies (EBs) composed of derivatives of all three embryonic germ layers. Customer Service and Ordering Information.Stroke: Vascular and Interventional Neurology.Journal of the American Heart Association (JAHA).Circ: Cardiovascular Quality & Outcomes.Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).
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