86
particularly for Iss and Ik1 in both animal models and for Ikslow PI3Kα mouse model.
Ito current density was not impacted by training or in PI3Kα mouse model compared
to control. In this study, this effect on repolarizing currents was accompanied by an
increase in L-type calcium current density in physiological hypertrophy and tran-
script analysis revealed an increased level of mRNA for Cav1.3, Cav β2, Cavα 2 δ1.
Other transcripts such as SCN5A and SCN1B coding for sodium channel alpha and
beta subunits were also upregulated. Finally, their study revealed that physiological
hypertrophy induces increase in repolarizing current without change in action poten-
tial properties. A hypothesis is that the increase in calcium current depolarizing cur-
rent balance the increased potassium current to maintain cardiomyocytes action
potential. However, another study using rats revealed that training had no effect on
ICaL current density [ 5 ]. Moreover, it was reported that trained rat displayed a
decreased APD, action potential amplitude and a slower dv/dt with a stable Ito potas-
sium current density [ 59 ]. This discrepancy clearly indicates that further studies are
need. One possibility to explain these differences is the different species (mice ver -
sus rats) and training protocol used. An interesting point was raised by the study of
Natali and colleagues [ 8 ]. Using trained rats, these authors highlighted the impor-
tance of the differences in cardiomyocytes electrophysiological properties depend-
ing on their tissue localization. They observed differences between the epicardium
and the endocardium for APD adaptation to chronic exercise. Training induced an
increase in APD in the epicardium and had no effects on the endocardium. This point
is important and it could explained discrepancy between studies that do not discrimi-
nate between endocardic and epicardic cardiomyocytes. As a consequence, it would
be very interesting to compare between these different cardiac locations the exercise
induced electrophysiological remodeling.
4 Conclusions
As shown in Fig. 5.1, summarizing the data is very difficult as numerous results
remain controversial. It should be noted that such a situation results from at least a
fundamental difficulty: in spite of the fact that cardiac hypertrophy under training is
a solid knowledge, this could not be true at the level of isolated cells (cardiomyo-
cytes) as other types of cells could contribute to the tissue hypertrophy. Despite the
lack of consensus, it has been shown that exercise training induced cardiomyocyte
hypertrophy (cell volume) although these changes were not clearly related to spe-
cific cell length or width modifications. Exercise training also induces contractile
and electrophysiological adaptations of healthy cardiomyocytes. Indeed, it has for
example been underlined an increase in the calcium transient kinetics or in the
expression of many proteins of the excitation-contraction coupling (SERCA2a,
PLB and RyR2) but also a decrease of the sparks frequency. Similarly, increased
current amplitude is, at least in part, compensated by the increase in cardiomyocyte
volume ensuring the good electrical activity of this remodeled cells. Beside, an
increase in repolarizing currents could also enhance the ability of the heart to
A. Krzesiak et al.