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.
Exercise training reduces resting heart rate via downregulation of the funny channel HCN4 / A. D'souza, A. Bucchi, A.B. Johnsen, S.J.R.J. Logantha, O. Monfredi, J. Yanni, S. Prehar, G. Hart, E. Cartwright, U. Wisloff, H. Dobryznski, D. Difrancesco, G.M. Morris, M.R. Boyett. - In: NATURE COMMUNICATIONS. - ISSN 2041-1723. - 5(2014), pp. 3775.1-3775.12.
|Titolo:||Exercise training reduces resting heart rate via downregulation of the funny channel HCN4|
BUCCHI, ANNALISA (Secondo)
|Parole Chiave:||CA2+-activated K+ channel; rabbit sinoatrial node; atrioventricular node; clinical-significance; cardiac fibroblasts; atrial-fibrillation; pacemaker activity; functional roles; sudden-death; follow-up|
|Settore Scientifico Disciplinare:||Settore BIO/09 - Fisiologia|
|Data di pubblicazione:||2014|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/ncomms4775|
|Appare nelle tipologie:||01 - Articolo su periodico|