Beta-adrenergic and muscarinic modulation of human embryonic stem cell-derived cardiomyocytes.
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, FP(slow), indicating a stimulation of Ca2+ channels in ventricular-like ES cell-derived cardiomyocytes which is shown to be clearly independent from frequency modulation. In contrast, carbachol (10 microM) produced a transient negative chronotropic effect but had no effect on FP(slow).


CONCLUSIONS
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.
Reppel
Michael
M
Institute of Neurophysiology, University of Cologne, Germany.
Boettinger
Cornelia
C
Hescheler
Juergen
J
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D004622:Embryo, Mammalian / Q000166:cytology*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008839:Microelectrodes; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology
D000318:Adrenergic beta-Agonists; D018727:Muscarinic Antagonists; D002217:Carbachol; D007545:Isoproterenol