Tampere University of Technology

TUTCRIS Research Portal

The Effects of Pharmacological Compounds on Beat Rate Variations in Human Long QT-Syndrome Cardiomyocytes

Research output: Contribution to journalArticleScientificpeer-review

Details

Original languageEnglish
Pages (from-to)698–707
Number of pages10
JournalStem Cell Reviews and Reports
Volume12
Issue number6
DOIs
Publication statusPublished - 2016
Publication typeA1 Journal article-refereed

Abstract

Healthy human heart rate fluctuates overtime showing long-range fractal correlations. In contrast, various cardiac diseases and normal aging show the breakdown of fractal complexity. Recently, it was shown that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) intrinsically exhibit fractal behavior as in humans. Here, we investigated the fractal complexity of hiPSC-derived long QT-cardiomyocytes (LQT-CMs). We recorded extracellular field potentials from hiPSC-CMs at baseline and under the effect of various compounds including β-blocker bisoprolol, ML277, a specific and potent IKs current activator, as well as JNJ303, a specific IKs blocker. From the peak-to-peak-intervals, we determined the long-range fractal correlations by using detrended fluctuation analysis. Electrophysiologically, the baseline corrected field potential durations (cFPDs) were more prolonged in LQT-CMs than in wildtype (WT)-CMs. Bisoprolol did not have significant effects to the cFPD in any CMs. ML277 shortened cFPD in a dose-dependent fashion by 11 % and 5–11 % in WT- and LQT-CMs, respectively. JNJ303 prolonged cFPD in a dose-dependent fashion by 22 % and 7–13 % in WT- and LQT-CMs, respectively. At baseline, all CMs showed fractal correlations as determined by short-term scaling exponent α. However, in all CMs, the α was increased when pharmacological compounds were applied indicating of breakdown of fractal complexity. These findings suggest that the intrinsic mechanisms contributing to the fractal complexity are not altered in LQT-CMs. The modulation of IKs channel and β1-adrenoreceptors by pharmacological compounds may affect the fractal complexity of the hiPSC-CMs.

ASJC Scopus subject areas

Keywords

  • Cardiomyocytes, Detrended fluctuation analysis, Fractals, Induced pluripotent stem cell, Long QT syndrome, Multielectrode array, Nonlinear dynamics

Publication forum classification

Field of science, Statistics Finland

Downloads statistics

No data available