Mechanism of automaticity in cardiomyocytes derived from human induced pluripotent stem cells

article i nfo Background and objectives. The creation of cardiomyocytes derived from human induced pluripotent stem cells (hiPS-CMs) has spawned broad excitement borne out of the prospects to diagnose and treat cardiovascular dis- eases based on personalized medicine. A common feature of hiPS-CMs is their spontaneous contractions but the mechanism(s) remain uncertain. Methods. Intrinsic activity was investigated by the voltage-clamp technique, optical mapping of action potentials (APs) and intracellular Ca 2+ (Cai )t ransients (CaiT) at subcellular- resolution and pharmacological interventions. Results. The frequency of spontaneous Cai T( sCaiT) in monolayers of hiPS-CMs was not altered by ivabradine, an inhibitor of the pacemaker current, If despite high levels of HCN transcripts (1-4). HiPS-CMs had negligible If and IK1 (inwardly-rectifying K + -current) and a minimum diastolic