Image-based evaluation of contraction-relaxation kinetics of human-induced pluripotent stem cell-derived cardiomyocytes: Correlation and complementarity with extracellular electrophysiology

J Mol Cell Cardiol. 2014 Dec:77:178-91. doi: 10.1016/j.yjmcc.2014.09.010. Epub 2014 Sep 23.

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.

Keywords: Ca(2+) transient; Field potential; Human-induced pluripotent stem cell-derived cardiomyocytes; Motion vector prediction; Multi-electrode arrays; Traction force microscopy.

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Biomechanical Phenomena
  • Calcium Channel Blockers / pharmacology
  • Calcium Signaling
  • Cell Differentiation
  • Cells, Cultured
  • Electrophysiologic Techniques, Cardiac
  • Humans
  • Induced Pluripotent Stem Cells / physiology*
  • Isoproterenol / pharmacology
  • Kinetics
  • Microscopy, Video
  • Myocardial Contraction*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / physiology*
  • Piperidines / pharmacology
  • Pyridines / pharmacology
  • Sodium Channel Blockers / pharmacology
  • Tetrodotoxin / pharmacology
  • Verapamil / pharmacology

Substances

  • Adrenergic beta-Agonists
  • Calcium Channel Blockers
  • Piperidines
  • Pyridines
  • Sodium Channel Blockers
  • E 4031
  • Tetrodotoxin
  • Verapamil
  • Isoproterenol