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Cell Physiol Biochem. 2004;14(4-6):187-96.

Beta-adrenergic and muscarinic modulation of human embryonic stem cell-derived cardiomyocytes.

Author information

1
Institute of Neurophysiology, University of Cologne, Germany.

Abstract

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).

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.

PMID:
15319521
DOI:
10.1159/000080326
[Indexed for MEDLINE]

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