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Received September 25, 2003
Revised October 23, 2003
Accepted after revision October 23, 2003
1 Dept. Pharmcology & Toxicology, Medical Faculty TU Dresden
2 Medical Clinics I, Medical Faculty TU Dresden
* To whom correspondence should be addressed. E-mail: ravens{at}rcs.urz.tu-dresden.de.
Human mesenchymal stem cells (hMSC) have gained
considerable interest due to their potential use for
cell replacement therapy and tissue engineering. One
strategy is to in vitro differentiate these bone marrow
stem cells into cardiomyocytes prior to implantation. In
this context ion channels can be important functional
markers of cardiac differentiation. At present there is
little information about the electrophysiological
behaviour of the undifferentiated hMSC. We therefore
investigated mRNA expression of 26 ion channel subunits
using semi-quantitative RT-PCR and recorded
transmembrane ion currents with the whole-cell voltage
clamp technique. Bone marrow hMSC were obtained from
healthy donors. The cells revealed a distinct pattern of
ion channel mRNA with high expression levels for some
channel subunits (e.g. Kv4.2, Kv4.3, MaxiK, HCN2, and
1C of the L-type calcium channel). Outward
currents were recorded in almost all cells. The most
abundant outward current rapidly activated at potentials
positive to +20 mV. This current was identified as a
large-conductance voltage- and Ca2+-activated
K+ current, conducted by MaxiK channels, due
to its high sensitivity to tetraethylammonium
(IC50 = 340 µM) and its inhibition by
100 nM
iberiotoxin. A large fraction of cells also demonstrated
a more slowly activating current at potentials positive
to -30 mV. This current was selectively inhibited by
clofilium (IC50 = 0.8 µM).
Ba2+ inward currents, stimulated by
1 µM BayK 8644 were found in a few cells, indicating
expression of functional L-type Ca2+
channels. Other inward currents like sodium currents or
inward rectifier currents were absent. We conclude that
undifferentiated hMSC express a distinct pattern of ion
channel mRNA and functional ion channels that might
contribute to physiological cell function.
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