Alicia D’Souza 1 , 4 , Annalisa Bucchi 2 , 4 , Anne Berit Johnsen 3 , 4 , Sunil Jit R.J. Logantha 1 , 4 , Oliver Monfredi 1 , Joseph Yanni 1 , Sukhpal Prehar 1 , George Hart 1 , Elizabeth Cartwright 1 , Ulrik Wisloff 3 , Halina Dobryznski a , 1 , Dario DiFrancesco 2 , Gwilym M. Morris 1 , Mark R. Boyett b , 1
13 May 2014
Endurance athletes exhibit sinus bradycardia, that is a slow resting heart rate, associated with a higher incidence of sinus node (pacemaker) disease and electronic pacemaker implantation. Here we show that training-induced bradycardia is not a consequence of changes in the activity of the autonomic nervous system but is caused by intrinsic electrophysiological changes in the sinus node. We demonstrate that training-induced bradycardia persists after blockade of the autonomous nervous system in vivo in mice and in vitro in the denervated sinus node. We also show that a widespread remodelling of pacemaker ion channels, notably a downregulation of HCN4 and the corresponding ionic current, I f. Block of I f abolishes the difference in heart rate between trained and sedentary animals in vivo and in vitro. We further observe training-induced downregulation of Tbx3 and upregulation of NRSF and miR-1 (transcriptional regulators) that explains the downregulation of HCN4. Our findings provide a molecular explanation for the potentially pathological heart rate adaptation to exercise training.
Endurance athletes are known to have a low resting heart rate. Here, D'Souza et al. propose that training-induced bradycardia is the result of electrophysiological changes in the sinus node, challenging the classical view that training-induced bradycardia is caused by increased activity of the autonomic nervous system.