Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 14, Issue 4-6, Pages 187-196Publisher
KARGER
DOI: 10.1159/000080326
Keywords
human embryonic stem cells; cardiomyocytes; heart; beta-adrenergic receptor; muscarinic receptor
Categories
Ask authors/readers for more resources
Background: Embryonic stem cells provide the most promising tool for cell replacement therapy including transplantation of human embryonic stem (hES) cell-derived cardiomyocytes in the infarcted area of the heart. Here we provide data for differentiation of cardiomyocytes from hES cells and firstly describe their hormonal modulation. Methods: Using Micro-Electrode Arrays as a novel electrical mapping technique of beating cardiomyocyte clusters within whole hES cell aggregates, we were able to measure the field potential generation and morphology changes during hormonal modulation. Results: We found that isoproterenol provokes, similar to the mouse ES cell system, a strong positive chronotropic effect with an EC50 of around 10(-8) M. Moreover, isoproterenol stimulated with a higher EC50 value the slow field potential amplitude, FPslow, indicating a stimulation of Ca2+ channels in ventricular-like ES cell-derived cardiomyocytes which is shown to be clearly independent from frequence modulating. In contrast, carbachol (10 muM) produced a transient negative chronotropic effect but had no effect on FPslow. Conclusion: The Micro-Electrode system allows measurement of ionic channel modulation and chronotropic responsiveness in a pharmacological screening setup. Moreover, all our data indicate that cardiomyocytes derived from human embryonic stem cells exhibit a physiological response to the major hormones of the vegetative nervous system and might therefore serve as an ideal candidate for the use in cell replacement strategies. Copyright (C) 2004 S. Karger AG, Basel.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available