IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms9803.html
   My bibliography  Save this article

Late Na+ current and protracted electrical recovery are critical determinants of the aging myopathy

Author

Listed:
  • Sergio Signore

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

  • Andrea Sorrentino

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

  • Giulia Borghetti

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

  • Antonio Cannata

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

  • Marianna Meo

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

  • Yu Zhou

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

  • Ramaswamy Kannappan

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

  • Francesco Pasqualini

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

  • Heather O'Malley

    (University of Michigan)

  • Mark Sundman

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

  • Nikolaos Tsigkas

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

  • Eric Zhang

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

  • Christian Arranto

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

  • Chiara Mangiaracina

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

  • Kazuya Isobe

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

  • Brena F. Sena

    (Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School)

  • Junghyun Kim

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

  • Polina Goichberg

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

  • Matthias Nahrendorf

    (Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School)

  • Lori L. Isom

    (University of Michigan)

  • Annarosa Leri

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

  • Piero Anversa

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

  • Marcello Rota

    (Brigham and Women’s Hospital, Harvard Medical School, 20 Shattuck Street, Boston, Massachusetts 02115, USA)

Abstract

The aging myopathy manifests itself with diastolic dysfunction and preserved ejection fraction. We raised the possibility that, in a mouse model of physiological aging, defects in electromechanical properties of cardiomyocytes are important determinants of the diastolic characteristics of the myocardium, independently from changes in structural composition of the muscle and collagen framework. Here we show that an increase in the late Na+ current (INaL) in aging cardiomyocytes prolongs the action potential (AP) and influences temporal kinetics of Ca2+ cycling and contractility. These alterations increase force development and passive tension. Inhibition of INaL shortens the AP and corrects dynamics of Ca2+ transient, cell contraction and relaxation. Similarly, repolarization and diastolic tension of the senescent myocardium are partly restored. Thus, INaL offers inotropic support, but negatively interferes with cellular and ventricular compliance, providing a new perspective of the biology of myocardial aging and the aetiology of the defective cardiac performance in the elderly.

Suggested Citation

  • Sergio Signore & Andrea Sorrentino & Giulia Borghetti & Antonio Cannata & Marianna Meo & Yu Zhou & Ramaswamy Kannappan & Francesco Pasqualini & Heather O'Malley & Mark Sundman & Nikolaos Tsigkas & Eri, 2015. "Late Na+ current and protracted electrical recovery are critical determinants of the aging myopathy," Nature Communications, Nature, vol. 6(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9803
    DOI: 10.1038/ncomms9803
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms9803
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms9803?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9803. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.