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 o...

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Bibliographic Details
Published in:	Journal of molecular and cellular cardiology 2014-12, Vol.77, p.178-191
Main Authors:	Hayakawa, Tomohiro, Kunihiro, Takeshi, Ando, Tomoko, Kobayashi, Seiji, Matsui, Eriko, Yada, Hiroaki, Kanda, Yasunari, Kurokawa, Junko, Furukawa, Tetsushi
Format:	Article
Language:	eng
Subjects:	Adrenergic beta-Agonists - pharmacology Biomechanical Phenomena Ca2 + transient Calcium Channel Blockers - pharmacology Calcium Signaling Cardiovascular Cell Differentiation Cells, Cultured Electrophysiologic Techniques, Cardiac Field potential Human-induced pluripotent stem cell-derived cardiomyocytes Humans Induced Pluripotent Stem Cells - physiology Isoproterenol - pharmacology Kinetics Microscopy, Video Motion vector prediction Multi-electrode arrays Myocardial Contraction Myocytes, Cardiac - drug effects Myocytes, Cardiac - physiology Piperidines - pharmacology Pyridines - pharmacology Sodium Channel Blockers - pharmacology Tetrodotoxin - pharmacology Traction force microscopy Verapamil - pharmacology
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Summary:	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 (30–150 nM), isoproterenol (0.1–10 μM) and E-4031 (10–50 nM). In addition, tetrodotoxin (3–30 μM)-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 100 nM 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.
ISSN:	0022-2828 1095-8584