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Exercise training reduces resting heart rate via downregulation of the funny channel HCN4.

ABSTRACT: 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, If. Block of If 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.

SUBMITTER: D'Souza A

PROVIDER: S-EPMC4024745 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Exercise training reduces resting heart rate via downregulation of the funny channel HCN4.

D'Souza Alicia A Bucchi Annalisa A Johnsen Anne Berit AB Logantha Sunil Jit R J SJ Monfredi Oliver O Yanni Joseph J Prehar Sukhpal S Hart George G Cartwright Elizabeth E Wisloff Ulrik U Dobryznski Halina H DiFrancesco Dario D Morris Gwilym M GM Boyett Mark R MR

Nature communications 20140513

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 ...[more]

PMID: 24825544

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Project description:This study investigates the effect of 6 weeks of supramaximal exercise training (SET) on heart rate variability (HRV) and associated factors in sedentary obese (OB) and normal-weight (NW) adults. In this study, 19 OB [22.9 (8.4) years; body mass index (BMI) 33.4 (1.4) kg/m2] and 18 NW [23.2 (4.4) years; BMI 23.3 (1.2) kg/m2] adults completed a 6-week SET intervention. Anthropometric and aerobic indicators as well the homeostasis model assessment index for insulin resistance index (HOMA-IR) were assessed at baseline and after SET. The low- and high-frequency [(LF (0.03-0.15 Hz) in ms2 and HF (0.15-0.4 Hz) in ms2)] analysis of HRV as well as adrenaline (A in nmol/l) and noradrenaline (NA in nmol/l) responses were assessed at resting condition and during ventilatory threshold 1 (VT1) of a graded maximal test at baseline and after SET. At baseline, resting HF, LF and the LF/HF ratio were different among groups (P < 0.01, respectively) and were significantly associated with waist-to-hip ratio (β = -0.26; p = 0.01, β = -0.12; p = 0.01 and, β = 0.21; p = 0.01). During exertion at VT1, only LF/HF ratio was associated with NA responses (β = 0.23; p = 0.01). After SET, the frequency domain marker improved significantly for both groups in comparison to baseline. These improvements are manifested by LF and HF increases and LF/HF ratio decreases in the rest condition (p < 0.01, respectively) and during exertion at VT1 (p < 0.01, respectively). The improvement in LH and HF were associated with VO2max increases (β = 0.22 p = 0.01 and β = 0.33; p = 0.01). The decreases observed for the LF/HF ratio are mainly associated to NA decreases observed at rest (β = 0.31; p = 0.001) and at VT1 (β = 0.38; p = 0.001). Obese adults have altered HRV, and 6 weeks of SET improves HRV variables at rest and during VT1 exertion. While LF and HF improvement were associated with VO2max increases, the LF/HF ratio was mainly associated with noradrenaline decreases observed at rest and at VT1.

Dataset Information

Exercise training reduces resting heart rate via downregulation of the funny channel HCN4.

Publications

Exercise training reduces resting heart rate via downregulation of the funny channel HCN4.

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