IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms5481.html
   My bibliography  Save this article

Modest CaV1.342-selective inhibition by compound 8 is β-subunit dependent

Author

Listed:
  • Hua Huang

    (Yong Loo Lin School of Medicine, National University of Singapore)

  • Cheng Yang Ng

    (National University of Singapore)

  • Dejie Yu

    (Yong Loo Lin School of Medicine, National University of Singapore)

  • Jing Zhai

    (Yong Loo Lin School of Medicine, National University of Singapore)

  • Yulin Lam

    (National University of Singapore)

  • Tuck Wah Soong

    (Yong Loo Lin School of Medicine, National University of Singapore
    NUS Graduate School for Integrative Sciences and Engineering
    Neurobiology/Ageing Programme, National University of Singapore
    National Neuroscience Institute, Jalan Tan Tock Seng)

Abstract

Two voltage-gated calcium channel subtypes—CaV1.2 and CaV1.3—underlie the major L-type Ca2+ currents in the mammalian central nervous system. Owing to their high sequence homology, the two channel subtypes share similar pharmacological properties, and at high doses classic calcium channel blockers, such as dihydropyridines, phenylalkylamines and benzothiazepines, do not discriminate between the two channel subtypes. Recent progress in treating Parkinson’s disease (PD) was marked by the discovery of synthetic compound 8, which was reported to be a highly selective inhibitor of the CaV1.3 L-type calcium channels (LTCC). However, despite a previously reported IC50 of ~24 μM, in our hands inhibition of the full-length CaV1.342 by compound 8 at 50 μM reaches a maximum of 45%. Moreover, we find that the selectivity of compound 8 towards CaV1.3 relative to CaV1.2B15 channels is greatly influenced by the β-subunit type and its splice isoform variants.

Suggested Citation

  • Hua Huang & Cheng Yang Ng & Dejie Yu & Jing Zhai & Yulin Lam & Tuck Wah Soong, 2014. "Modest CaV1.342-selective inhibition by compound 8 is β-subunit dependent," Nature Communications, Nature, vol. 5(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5481
    DOI: 10.1038/ncomms5481
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms5481
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms5481?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Pietro Mesirca & Jean Chemin & Christian Barrère & Eleonora Torre & Laura Gallot & Arnaud Monteil & Isabelle Bidaud & Sylvie Diochot & Michel Lazdunski & Tuck Wah Soong & Stéphanie Barrère-Lemaire & M, 2024. "Selective blockade of Cav1.2 (α1C) versus Cav1.3 (α1D) L-type calcium channels by the black mamba toxin calciseptine," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

    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:5:y:2014:i:1:d:10.1038_ncomms5481. 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.