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Development of electrical activity in cardiac myocyte aggregates derived from mouse embryonic stem cells.
Banach K, Halbach MD, Hu P, Hescheler J, Egert U.
Institut fur Neurophysiologie, Universitat zu Koln, Germany. kbanac1@lumc.edu
Embryonic
stem cells differentiate into cardiac myocytes, repeating in vitro the
structural and molecular changes associated with cardiac development.
Currently, it is not clear whether the electrophysiological properties
of the multicellular cardiac structure follow cardiac maturation as
well. In long-term recordings of extracellular field potentials with
microelectrode arrays consisting of 60 substrate-integrated electrodes,
we examined the electrophysiological properties during the ongoing
differentiation process. The beating frequency of the growing
preparations increased from 1 to 5 Hz concomitant to a decrease of the
action potential duration and action potential rise time. A
developmental increase of the conduction velocity could be attributed
to an increased expression of connexin43 gap junction channels. Whereas
isoprenalin elicited a positive chronotropic response from the first
day of spontaneous beating onward, a concentration-dependent negative
chronotropic effect of carbachol only developed after approximately 4
days. The in vitro development of the three-dimensional cardiac
preparation thus closely follows the development described for the
mouse embryonic heart, making it an ideal model to monitor the
differentiation of electrical activity in embryonic cardiomyocytes.
PMID: 12573993 [PubMed - indexed for MEDLINE]
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