Biomedical Engineering Reference
In-Depth Information
type cells and that during the process of maturation the loss of sinus node type
I
f
current and the gain of inward rectifier current (
I
K1
) [12, 67] results in the loss of
intrinsic automaticity.
Fig. 2.
Order by which membrane currents develop in the murine embryonic ventricle (
arrow
at top
). During remodeling in pathophysiological processes these currents might reappear in
reverse order (
arrow at bottom
). Reproduced with permission from [67].
2.5 ß-Adrenergic Modulation of Currents in Embryonic Myocytes
As early as at 9.5 dpc
I
f
current is responsive to ß-adrenergic modulation [66], as is
the case with the L-type Ca
2+
current [30]. The fact that
I
f
is more responsive to
forskolin than to isoproterenol [66] suggests that the intracellular second messenger
cascade develops earlier than (coupling to) the ß-adrenoceptor in the sarcolemma.
Directly after birth the responsiveness to ß-adrenergic stimulation continues to
increase as has been demonstrated in chicken [56].
Interestingly, in cardiomyocytes differentiated from human embryonic stem cells,
positive chronotropic effects have been reported in response to phenylephrine
(10
-4
M), an Į-adrenergic agonist, and to isoprenaline (10
-6
M), a ß-adrenergic agonist.
Also, negative effects of exposure to carbachol (10
-4
M) were reported, which suggests
effective vagal responsiveness [38]. However, the concentrations of all these
substances were very high.
