Article citationsMore>>

Yamazaki, K., Hihara, T., Kato, H., Fukushima, T., Fukushima, K., Taniguchi, T., Yoshinaga, T., Miyamoto, N., Ito, M. and Sawada, K. (2014) Beat-to-Beat Variability in Field Potential Duration in Human Embryonic Stem Cell-Derived Cardiomyocyte Clusters for Assessment of Arrhythmogenic Risk, and a Case Study of Its Application. Pharmacology and Pharmacy, 5, 117-128. http://dx.doi.org/10.4236/pp.2014.51017

has been cited by the following article:

• TITLE: Use of Human Embryonic Stem Cell-Derived Cardiomyocyte Clusters to Assess Potential for Chronic Treatment with Compounds to Cause QT Prolongation

  AUTHORS: Taro Hihara, Kazuto Yamazaki, Tomohiko Taniguchi, Takashi Yoshinaga, Masashi Ito, Kohei Sawada

  KEYWORDS: Human Embryonic Stem Cell-Derived Cardiomyocytes; Field Potential Duration; QT Prolongation; Chronic Treatment; Risk Assessment

  JOURNAL NAME: Pharmacology & Pharmacy, Vol.5 No.4, April 9, 2014

  ABSTRACT: Drug-induced QT prolongation is a serious clinical issue in developing novel drug candidates and marketing drugs. A major cause of QT prolongation is direct inhibition of human ether-à-go-go-related gene (hERG) channels. Reduction in repolarization-related channel expression levels on plasma membranes is another mechanism that induces QT prolongation. Recently, we established a system for assessing the risk of QT prolongation by using human embryonic stem cell-derived cardiomyocyte clusters (hES-CMCs) in which the field potential duration (FPD) or corrected FPD (FPDc) was measured as an indicator of drug-induced QT interval prolongation. Here, we examined whether this system was able to detect FPDc prolongation caused by pentamidine or probucol, both of which can induce QT prolongation after long-term treatment. hES-CMCs were treated with pentamidine or probucol, and the FPDc of the same clusters was measured 10 min, 4 h, and 24 h after the start of treatment. Concentration-dependent FPDc prolongation was observed at 24 h, but not at 10 min, with pentamidine or probucol treatment. These results suggest that the hES-CMC-based assessment system can be used to detect both acute (at 10 min) and delayed (at 24 h) QT prolongation risk on the same platform by simple alteration of the extended culture period.