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sparks are local increase of Ca2+ elicited by synchronized opening of RyR2, at rest,
without excitation by L-type Ca2+ channels current. An excessive increase in spon-
taneous Ca2+ sparks could generate Ca2+ waves producing abnormal cardiac electri-
cal activity and reflected an impaired working of RyR2. Shao and colleagues [ 44 ]
and Carneiro-Junior and co-workers [ 45 ] reported both a decrease in frequency and
an increase in amplitude of spontaneous Ca2+ sparks in ventricular isolated myo-
cytes after moderate intensity continuous training of rats. Exercise training seems
to promote the closed state of RyR2 which is participating to normal working of
CRUs and is essential to local control of Ca2+ release during excitation-contraction
coupling.
3 Electrophysiological Remodeling Under Exercise Trainings
In addition to adaptation of calcium homeostasis and structural remodeling, training
induced physiological hypertrophy could also impact cardiac electrical activity [ 48 ,
49 ]. It is therefore important to understand the cellular and molecular determinants
that underlie these electrophysiological remodeling.
3.1 Electrophysiological Effects in Sinus
Chronic exercise is well known to induce sinus bradycardia, characterized by a
decrease in resting heart rate below 60 bpm [ 50 , 51 ]. Whereas bradycardia is
widely attributed to autonomous nervous system adaptation to chronic exercise,
experiments that block autonomous pathways or that use denervated sinus node
still observed a decrease in resting heart rate [ 52 , 53 ]. This suggest that the sinus
node, the cardiac pacemaker, is also impacted by exercise. Many ion channels par-
ticipate to the action potential of nodal cells. Amongst them, HCN channels and
particularly HCN4 support the funny current (If) current that control, at least in
part, the pacemaker activity [ 54 ]. To date, only one study investigated electrophysi-
ological remodeling of nodal cells using trained rat and mice compared to seden-
tary animals [ 53 ]. Interestingly, D’Souza and colleagues [ 53 ] reported that chronic
exercise induces a decrease in HCN4 channels. This decrease was observed at the
mRNA, protein and functional levels through a decrease in If current density in
freshly isolated nodal cells of trained animal compared to the control group.
Furthermore, they highlighted the correlation between the decrease in heart rate or
in Vo2max and the decrease of HCN4 mRNA. These results were confirmed in vivo
using Ivabradine, a specific blocker of If [ 55 ] that produced a less important reduc-
tion in heart rate for trained animals. Interestingly, the bradycardic effect of chronic
exercise was reversed when mice were detrained for 2 weeks and this was associ-
ated to a marked increase in HCN4 mRNA. To date, this is the only study in our
knowledge that investigated the bradycardic effect of chronic exercise on sinus
A. Krzesiak et al.