title: Image-based evaluation of contraction-relaxation kinetics of human-induced pluripotent stem cell-derived cardiomyocytes: Correlation and complementarity with extracellular electrophysiology.
abstract: In this study, we used high-speed video microscopy with motion vector analysis to investigate the contractile characteristics of hiPS-CM monolayer, in addition to further characterizing the motion with extracellular field potential (FP), traction force and the Ca(2+) transient. Results of our traction force microscopy demonstrated that the force development of hiPS-CMs correlated well with the cellular deformation detected by the video microscopy with motion vector analysis. In the presence of verapamil and isoproterenol, contractile motion of hiPS-CMs showed alteration in accordance with the changes in fluorescence peak of the Ca(2+) transient, i.e., upstroke, decay, amplitude and full-width at half-maximum. Simultaneously recorded hiPS-CM motion and FP showed that there was a linear correlation between changes in the motion and field potential duration in response to verapamil (30-150nM), isoproterenol (0.1-10μM) and E-4031 (10-50nM). In addition, tetrodotoxin (3-30μM)-induced delay of sodium current was corresponded with the delay of the contraction onset of hiPS-CMs. These results indicate that the electrophysiological and functional behaviors of hiPS-CMs are quantitatively reflected in the contractile motion detected by this image-based technique. In the presence of 100nM E-4031, the occurrence of early after-depolarization-like negative deflection in FP was also detected in the hiPS-CM motion as a characteristic two-step relaxation pattern. These findings offer insights into the interpretation of the motion kinetics of the hiPS-CMs, and are relevant for understanding electrical and mechanical relationship in hiPS-CMs.
authors.affiliation: Medical Business Unit, Sony Corporation, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. Electronic address: tomohiro.hayakawa@jp.sony.com.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Hayakawa
authors.affiliation: Medical Business Unit, Sony Corporation, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kunihiro
authors.affiliation: Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ando
authors.affiliation: Medical Business Unit, Sony Corporation, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Medical Business Unit, Sony Corporation, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Matsui
authors.affiliation: Medical Business Unit, Sony Corporation, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yada
authors.affiliation: Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Kanda
authors.affiliation: Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Kurokawa
authors.affiliation: Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. Electronic address: t_furukawa.bip@mri.tmd.ac.jp.
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D001696:Biomechanical Phenomena; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling; D002454:Cell Differentiation; D002478:Cells, Cultured; D022062:Electrophysiologic Techniques, Cardiac; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D018715:Microscopy, Video; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D002121:Calcium Channel Blockers; D010880:Piperidines; D011725:Pyridines; D026941:Sodium Channel Blockers; C063968:E 4031; D013779:Tetrodotoxin; D014700:Verapamil; D007545:Isoproterenol
keywords: Ca(2+) transient; Field potential; Human-induced pluripotent stem cell-derived cardiomyocytes; Motion vector prediction; Multi-electrode arrays; Traction force microscopy