IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-18947-y.html
   My bibliography  Save this article

AKAP5 complex facilitates purinergic modulation of vascular L-type Ca2+ channel CaV1.2

Author

Listed:
  • Maria Paz Prada

    (University of California Davis)

  • Arsalan U. Syed

    (University of California Davis)

  • Gopireddy R. Reddy

    (University of California Davis)

  • Miguel Martín-Aragón Baudel

    (University of California Davis)

  • Víctor A. Flores-Tamez

    (University of California Davis)

  • Kent C. Sasse

    (Sasse Surgical Associates)

  • Sean M. Ward

    (University of Nevada Reno)

  • Padmini Sirish

    (University of California Davis)

  • Nipavan Chiamvimonvat

    (University of California Davis
    University of California Davis
    VA Northern California Healthcare System)

  • Peter Bartels

    (University of California Davis)

  • Eamonn J. Dickson

    (University of California Davis)

  • Johannes W. Hell

    (University of California Davis)

  • John D. Scott

    (University of Washington Seattle)

  • Luis F. Santana

    (University of California Davis)

  • Yang K. Xiang

    (University of California Davis
    VA Northern California Healthcare System)

  • Manuel F. Navedo

    (University of California Davis)

  • Madeline Nieves-Cintrón

    (University of California Davis)

Abstract

The L-type Ca2+ channel CaV1.2 is essential for arterial myocyte excitability, gene expression and contraction. Elevations in extracellular glucose (hyperglycemia) potentiate vascular L-type Ca2+ channel via PKA, but the underlying mechanisms are unclear. Here, we find that cAMP synthesis in response to elevated glucose and the selective P2Y11 agonist NF546 is blocked by disruption of A-kinase anchoring protein 5 (AKAP5) function in arterial myocytes. Glucose and NF546-induced potentiation of L-type Ca2+ channels, vasoconstriction and decreased blood flow are prevented in AKAP5 null arterial myocytes/arteries. These responses are nucleated via the AKAP5-dependent clustering of P2Y11/ P2Y11-like receptors, AC5, PKA and CaV1.2 into nanocomplexes at the plasma membrane of human and mouse arterial myocytes. Hence, data reveal an AKAP5 signaling module that regulates L-type Ca2+ channel activity and vascular reactivity upon elevated glucose. This AKAP5-anchored nanocomplex may contribute to vascular complications during diabetic hyperglycemia.

Suggested Citation

  • Maria Paz Prada & Arsalan U. Syed & Gopireddy R. Reddy & Miguel Martín-Aragón Baudel & Víctor A. Flores-Tamez & Kent C. Sasse & Sean M. Ward & Padmini Sirish & Nipavan Chiamvimonvat & Peter Bartels & , 2020. "AKAP5 complex facilitates purinergic modulation of vascular L-type Ca2+ channel CaV1.2," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18947-y
    DOI: 10.1038/s41467-020-18947-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-18947-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-18947-y?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:11:y:2020:i:1:d:10.1038_s41467-020-18947-y. 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.