Biomedical Engineering Reference
In-Depth Information
Fig. 5.
Summary of the expression of various ion channels during the differentiation process in
CMG cells
4 Discussion
The present study demonstrated that (1) bone marrow mesenchymal stem cells could
differentiate into cardiomyocytes with automaticity, (2) these cells expressed
ȕ
-adrenergic receptors and increased their beat rate in response to isoproterenol, and
(3) the transplanted cardiomyocytes survived in the recipient heart and connected to
the surrounding recipient cardiomyocytes via intercalated discs. We also found that
the action potentials of the bone marrow-derived cardiomyocytes changed progres-
sively with time. The temporal changes in action potentials occurred in parallel with
the serial expression of various ion channels. Ion channels mediating
I
K1
and
I
Kr
were
expressed prior to cardiomyocyte differentiation, suggesting that they were functional
in the mesenchymal stem cells themselves or in both cardiomyocyte and nonmyocyte
derivatives. During differentiation, the ion channels responsible for
I
Ca,L
and If were
expressed first, followed by the ion channels that mediate
I
to
and
I
K,ATP
. These findings
strongly suggest that the differential expression of ion channels produced the temporal
changes in action potentials.
Interestingly, bone marrow-derived cardiomyocytes expressed the pacemaker ion
channels HCN4 after 2 weeks and HCN2 after 6 weeks. Moreover, they showed
automaticity from 2 weeks, suggesting that HCN4 might be involved in the induction
of automaticity. These findings suggest that they might be used as a bio-pacemaker
when transplanted [28, 31]. The present study did not attempt to make sinoatrial or
atrioventricular blocks, because the mice were too small for this to be practicable.
