1. Neuroscience
  2. Physics of Living Systems
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Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure

Research Article
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Cite this article as: eLife 2018;7:e42628 doi: 10.7554/eLife.42628

Abstract

Systemic blood pressure is determined, in part, by arterial smooth muscle cells (myocytes). Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and contribute to hypertension in vivo. We generated the first inducible, smooth muscle-specific knockout mice for a TRP channel, namely for PKD2 (TRPP1), to investigate arterial myocyte and blood pressure regulation by this protein. Using this model, we show that intravascular pressure and α1-adrenoceptors activate PKD2 channels in arterial myocytes of different systemic organs. PKD2 channel activation in arterial myocytes leads to an inward Na+ current, membrane depolarization and vasoconstriction. Inducible, smooth muscle cell-specific PKD2 knockout lowers both physiological blood pressure and hypertension and prevents pathological arterial remodeling during hypertension. Thus, arterial myocyte PKD2 controls systemic blood pressure and targeting this TRP channel reduces high blood pressure.

Article and author information

Author details

  1. Simon Bulley

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Carlos Fernández-Peña

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Raquibul Hasan

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. M Dennis Leo

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Padmapriya Muralidharan

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Charles E Mackay

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Kirk W Evanson

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Luiz Moreira-Junior

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Alejandro Mata-Daboin

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Sarah K Burris

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Qian Wang

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Korah P Kuruvilla

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Jonathan H Jaggar

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    For correspondence
    jjaggar@uthsc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1505-3335

Funding

National Heart, Lung, and Blood Institute (HL67061)

  • Jonathan H Jaggar

National Heart, Lung, and Blood Institute (HL133256)

  • Jonathan H Jaggar

National Heart, Lung, and Blood Institute (HL137745)

  • Jonathan H Jaggar

American Heart Association (16SDG27460007)

  • Simon Bulley

American Heart Association (15SDG22680019)

  • M Dennis Leo

American Heart Association (16POST30960010)

  • Raquibul Hasan

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to an approved institutional animal care and use committee (IACUC) protocol (#17-068.0) of the University of Tennessee. Every effort was made to minimize suffering.

Reviewing Editor

  1. Kenton Jon Swartz, National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States

Publication history

  1. Received: October 5, 2018
  2. Accepted: November 22, 2018
  3. Accepted Manuscript published: December 4, 2018 (version 1)
  4. Version of Record published: December 5, 2018 (version 2)

Copyright

© 2018, Bulley et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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