title: High purity human-induced pluripotent stem cell-derived cardiomyocytes: electrophysiological properties of action potentials and ionic currents.
abstract: Human-induced pluripotent stem cells (hiPSCs) can differentiate into functional cardiomyocytes; however, the electrophysiological properties of hiPSC-derived cardiomyocytes have yet to be fully characterized. We performed detailed electrophysiological characterization of highly pure hiPSC-derived cardiomyocytes. Action potentials (APs) were recorded from spontaneously beating cardiomyocytes using a perforated patch method and had atrial-, nodal-, and ventricular-like properties. Ventricular-like APs were more common and had maximum diastolic potentials close to those of human cardiac myocytes, AP durations were within the range of the normal human electrocardiographic QT interval, and APs showed expected sensitivity to multiple drugs (tetrodotoxin, nifedipine, and E4031). Early afterdepolarizations (EADs) were induced with E4031 and were bradycardia dependent, and EAD peak voltage varied inversely with the EAD take-off potential. Gating properties of seven ionic currents were studied including sodium (I(Na)), L-type calcium (I(Ca)), hyperpolarization-activated pacemaker (I(f)), transient outward potassium (I(to)), inward rectifier potassium (I(K1)), and the rapidly and slowly activating components of delayed rectifier potassium (I(Kr) and I(Ks), respectively) current. The high purity and large cell numbers also enabled automated patch-clamp analysis. We conclude that these hiPSC-derived cardiomyocytes have ionic currents and channel gating properties underlying their APs and EADs that are quantitatively similar to those reported for human cardiac myocytes. These hiPSC-derived cardiomyocytes have the added advantage that they can be used in high-throughput assays, and they have the potential to impact multiple areas of cardiovascular research and therapeutic applications.
authors: Cellular Dynamics International, Madison, Wisconsin, USA.
authors: Junyi
authors: J
authors: Ma
authors: Liang
authors: L
authors: Guo
authors: Steve J
authors: SJ
authors: Fiene
authors: Blake D
authors: BD
authors: Anson
authors: James A
authors: JA
authors: Thomson
authors: Timothy J
authors: TJ
authors: Kamp
authors: Kyle L
authors: KL
authors: Kolaja
authors: Bradley J
authors: BJ
authors: Swanson
authors: Craig T
authors: CT
authors: January
mesh_terms: D000200:Action Potentials; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D056966:Excitation Contraction Coupling / Q000187:drug effects; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006339:Heart Rate; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism*; D015640:Ion Channel Gating; D017136:Ion Transport; D007700:Kinetics; D049990:Membrane Transport Modulators / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D049990:Membrane Transport Modulators; D015221:Potassium Channels; D015222:Sodium Channels; D012964:Sodium; D011188:Potassium; D002118:Calcium