Blog
About

  • Record: found
  • Abstract: found
  • Article: found
Is Open Access

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

Read this article at

Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      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.

      Abstract

      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.

      Related collections

      Most cited references 60

      • Record: found
      • Abstract: found
      • Article: not found

      Structural and functional characterisation of cardiac fibroblasts.

      Cardiac fibroblasts form one of the largest cell populations, in terms of cell numbers, in the heart. They contribute to structural, biochemical, mechanical and electrical properties of the myocardium. Nonetheless, they are often disregarded by in vivo and in vitro studies into cardiac function. This review summarizes our understanding of fibroblast origin and identity, their structural organization and role in myocardial architecture, as well as functional aspects related to cell signalling and electro-mechanical function in the heart.
        Bookmark
        • Record: found
        • Abstract: found
        • Article: not found

        Does sports activity enhance the risk of sudden death in adolescents and young adults?

        We sought to assess the risk of sudden death (SD) in both male and female athletes age 12 to 35 years. Little is known about the risk of SD in adolescents and young adults engaged in sports. We did a 21-year prospective cohort study of all young people of the Veneto Region of Italy. From 1979 to 1999, the total population of adolescents and young adults averaged 1,386,600 (692,100 males and 694,500 females), of which 112,790 (90,690 males and 22,100 females) were competitive athletes. An analysis by gender of risk of SD and underlying pathologic substrates was performed in the athletic and non-athletic populations. There were 300 cases of SD, producing an overall cohort incidence rate of 1 in 100,000 persons per year. Fifty-five SDs occurred among athletes (2.3 in 100,000 per year) and 245 among non-athletes (0.9 in 100,000 per year), with an estimated relative risk (RR) of 2.5 (95% confidence interval [CI] 1.8 to 3.4; p < 0.0001). The RR of SD among athletes versus non-athletes was 1.95 (CI 1.3 to 2.6; p = 0.0001) for males and 2.00 (CI 0.6 to 4.9; p = 0.15) for females. The higher risk of SD in athletes was strongly related to underlying cardiovascular diseases such as congenital coronary artery anomaly (RR 79, CI 10 to 3,564; p < 0.0001), arrhythmogenic right ventricular cardiomyopathy (RR 5.4, CI 2.5 to 11.2; p < 0.0001), and premature coronary artery disease (RR 2.6, CI 1.2 to 5.1; p = 0.008). Sports activity in adolescents and young adults was associated with an increased risk of SD, both in males and females. Sports, per se, was not a cause of the enhanced mortality, but it triggered SD in those athletes who were affected by cardiovascular conditions predisposing to life-threatening ventricular arrhythmias during physical exercise.
          Bookmark
          • Record: found
          • Abstract: not found
          • Article: not found

          Ventricular remodeling after infarction and the extracellular collagen matrix: when is enough enough?

           B Jugdutt (2003)
            Bookmark

            Author and article information

            Affiliations
            [1 ]Institute of Cardiovascular Sciences, University of Manchester , Manchester M13 9NT, UK
            [2 ]Department of Biosciences, University of Milano , Milano 20133, Italy
            [3 ]Department of Circulation and Medical Imaging, Norwegian University of Science and Technology , Trondheim 7491, Norway
            [4 ]These authors contributed equally to this work
            Author notes
            Journal
            Nat Commun
            Nat Commun
            Nature Communications
            Nature Pub. Group
            2041-1723
            13 May 2014
            : 5
            24825544
            4024745
            ncomms4775
            10.1038/ncomms4775
            Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

            This work is licensed under a Creative Commons Attribution 3.0 Unported License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/

            Categories
            Article

            Uncategorized

            Comments

            Comment on this article