IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms7081.html
   My bibliography  Save this article

The mitochondrial uniporter controls fight or flight heart rate increases

Author

Listed:
  • Yuejin Wu

    (Carver College of Medicine, The University of Iowa
    Present address: Department of Medicine, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA)

  • Tyler P. Rasmussen

    (Carver College of Medicine, The University of Iowa
    Carver College of Medicine, The University of Iowa)

  • Olha M Koval

    (Carver College of Medicine, The University of Iowa)

  • Mei-ling A. Joiner

    (Carver College of Medicine, The University of Iowa)

  • Duane D. Hall

    (Carver College of Medicine, The University of Iowa)

  • Biyi Chen

    (Carver College of Medicine, The University of Iowa)

  • Elizabeth D. Luczak

    (Carver College of Medicine, The University of Iowa
    Present address: Department of Medicine, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA)

  • Qiongling Wang

    (Cardiovascular Research Institute, Baylor College of Medicine)

  • Adam G. Rokita

    (Carver College of Medicine, The University of Iowa
    University Hospital Regensburg)

  • Xander H.T. Wehrens

    (Cardiovascular Research Institute, Baylor College of Medicine)

  • Long-Sheng Song

    (Carver College of Medicine, The University of Iowa)

  • Mark E. Anderson

    (Carver College of Medicine, The University of Iowa
    Carver College of Medicine, The University of Iowa
    Present address: Department of Medicine, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA)

Abstract

Heart rate increases are a fundamental adaptation to physiological stress, while inappropriate heart rate increases are resistant to current therapies. However, the metabolic mechanisms driving heart rate acceleration in cardiac pacemaker cells remain incompletely understood. The mitochondrial calcium uniporter (MCU) facilitates calcium entry into the mitochondrial matrix to stimulate metabolism. We developed mice with myocardial MCU inhibition by transgenic expression of a dominant-negative (DN) MCU. Here, we show that DN-MCU mice had normal resting heart rates but were incapable of physiological fight or flight heart rate acceleration. We found that MCU function was essential for rapidly increasing mitochondrial calcium in pacemaker cells and that MCU-enhanced oxidative phoshorylation was required to accelerate reloading of an intracellular calcium compartment before each heartbeat. Our findings show that MCU is necessary for complete physiological heart rate acceleration and suggest that MCU inhibition could reduce inappropriate heart rate increases without affecting resting heart rate.

Suggested Citation

  • Yuejin Wu & Tyler P. Rasmussen & Olha M Koval & Mei-ling A. Joiner & Duane D. Hall & Biyi Chen & Elizabeth D. Luczak & Qiongling Wang & Adam G. Rokita & Xander H.T. Wehrens & Long-Sheng Song & Mark E., 2015. "The mitochondrial uniporter controls fight or flight heart rate increases," Nature Communications, Nature, vol. 6(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7081
    DOI: 10.1038/ncomms7081
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms7081
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms7081?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_ncomms7081. 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.