IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-023-43502-w.html
   My bibliography  Save this article

Selective blockade of Cav1.2 (α1C) versus Cav1.3 (α1D) L-type calcium channels by the black mamba toxin calciseptine

Author

Listed:
  • Pietro Mesirca

    (Université de Montpellier, CNRS, INSERM
    Laboratory of Excellence Ion Channels, Science & Therapeutics)

  • Jean Chemin

    (Université de Montpellier, CNRS, INSERM
    Laboratory of Excellence Ion Channels, Science & Therapeutics)

  • Christian Barrère

    (Université de Montpellier, CNRS, INSERM
    Laboratory of Excellence Ion Channels, Science & Therapeutics)

  • Eleonora Torre

    (Université de Montpellier, CNRS, INSERM
    Laboratory of Excellence Ion Channels, Science & Therapeutics)

  • Laura Gallot

    (Université de Montpellier, CNRS, INSERM
    Laboratory of Excellence Ion Channels, Science & Therapeutics)

  • Arnaud Monteil

    (Université de Montpellier, CNRS, INSERM
    Laboratory of Excellence Ion Channels, Science & Therapeutics
    Mahidol University)

  • Isabelle Bidaud

    (Université de Montpellier, CNRS, INSERM
    Laboratory of Excellence Ion Channels, Science & Therapeutics)

  • Sylvie Diochot

    (Laboratory of Excellence Ion Channels, Science & Therapeutics
    Université Côte d’Azur, CNRS, IPMC (Institut de Pharmacologie Moléculaire et Cellulaire), FHU InovPain (Fédération Hospitalo-Universitaire “Innovative Solutions in Refractory Chronic Pain”))

  • Michel Lazdunski

    (Laboratory of Excellence Ion Channels, Science & Therapeutics
    Université Côte d’Azur, CNRS, IPMC (Institut de Pharmacologie Moléculaire et Cellulaire), FHU InovPain (Fédération Hospitalo-Universitaire “Innovative Solutions in Refractory Chronic Pain”))

  • Tuck Wah Soong

    (National University of Singapore)

  • Stéphanie Barrère-Lemaire

    (Université de Montpellier, CNRS, INSERM
    Laboratory of Excellence Ion Channels, Science & Therapeutics)

  • Matteo E. Mangoni

    (Université de Montpellier, CNRS, INSERM
    Laboratory of Excellence Ion Channels, Science & Therapeutics)

  • Joël Nargeot

    (Université de Montpellier, CNRS, INSERM
    Laboratory of Excellence Ion Channels, Science & Therapeutics)

Abstract

L-type voltage-gated calcium channels are involved in multiple physiological functions. Currently available antagonists do not discriminate between L-type channel isoforms. Importantly, no selective blocker is available to dissect the role of L-type isoforms Cav1.2 and Cav1.3 that are concomitantly co-expressed in the heart, neuroendocrine and neuronal cells. Here we show that calciseptine, a snake toxin purified from mamba venom, selectively blocks Cav1.2 -mediated L-type calcium currents (ICaL) at concentrations leaving Cav1.3-mediated ICaL unaffected in both native cardiac myocytes and HEK-293T cells expressing recombinant Cav1.2 and Cav1.3 channels. Functionally, calciseptine potently inhibits cardiac contraction without altering the pacemaker activity in sino-atrial node cells, underscoring differential roles of Cav1.2− and Cav1.3 in cardiac contractility and automaticity. In summary, calciseptine is a selective L-type Cav1.2 Ca2+ channel blocker and should be a valuable tool to dissect the role of these L-channel isoforms.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-43502-w
    DOI: 10.1038/s41467-023-43502-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43502-w
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-43502-w?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
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. Jaime N. Guzman & Javier Sanchez-Padilla & David Wokosin & Jyothisri Kondapalli & Ema Ilijic & Paul T. Schumacker & D. James Surmeier, 2010. "Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1," Nature, Nature, vol. 468(7324), pages 696-700, December.
    3. Soosung Kang & Garry Cooper & Sara F. Dunne & Brendon Dusel & Chi-Hao Luan & D. James Surmeier & Richard B. Silverman, 2012. "CaV1.3-selective L-type calcium channel antagonists as potential new therapeutics for Parkinson's disease," Nature Communications, Nature, vol. 3(1), pages 1-7, January.
    4. Nadine J. Ortner & Gabriella Bock & David H.F. Vandael & Robert Mauersberger & Henning J. Draheim & Ronald Gust & Emilio Carbone & Petronel Tuluc & Jörg Striessnig, 2014. "Pyrimidine-2,4,6-triones are a new class of voltage-gated L-type Ca2+ channel activators," Nature Communications, Nature, vol. 5(1), pages 1-10, September.
    5. Sylvie Diochot & Anne Baron & Miguel Salinas & Dominique Douguet & Sabine Scarzello & Anne-Sophie Dabert-Gay & Delphine Debayle & Valérie Friend & Abdelkrim Alloui & Michel Lazdunski & Eric Lingueglia, 2012. "Black mamba venom peptides target acid-sensing ion channels to abolish pain," Nature, Nature, vol. 490(7421), pages 552-555, October.
    6. Donald M. Bers, 2002. "Cardiac excitation–contraction coupling," Nature, Nature, vol. 415(6868), pages 198-205, January.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Quanxia Lyu & Shu Gong & Jarmon G. Lees & Jialiang Yin & Lim Wei Yap & Anne M. Kong & Qianqian Shi & Runfang Fu & Qiang Zhu & Ash Dyer & Jennifer M. Dyson & Shiang Y. Lim & Wenlong Cheng, 2022. "A soft and ultrasensitive force sensing diaphragm for probing cardiac organoids instantaneously and wirelessly," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Hongyan Gao & Zhien Wang & Feiyu Yang & Xiaoyu Wang & Siqi Wang & Quan Zhang & Xiaomeng Liu & Yubing Sun & Jing Kong & Jun Yao, 2024. "Graphene-integrated mesh electronics with converged multifunctionality for tracking multimodal excitation-contraction dynamics in cardiac microtissues," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    3. Roman Nikolaienko & Elisa Bovo & Daniel Kahn & Ryan Gracia & Thomas Jamrozik & Aleksey V. Zima, 2023. "Cysteines 1078 and 2991 cross-linking plays a critical role in redox regulation of cardiac ryanodine receptor (RyR)," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    4. Marco C. Miotto & Steven Reiken & Anetta Wronska & Qi Yuan & Haikel Dridi & Yang Liu & Gunnar Weninger & Carl Tchagou & Andrew R. Marks, 2024. "Structural basis for ryanodine receptor type 2 leak in heart failure and arrhythmogenic disorders," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Brett Volmert & Artem Kiselev & Aniwat Juhong & Fei Wang & Ashlin Riggs & Aleksandra Kostina & Colin O’Hern & Priyadharshni Muniyandi & Aaron Wasserman & Amanda Huang & Yonatan Lewis-Israeli & Vishal , 2023. "A patterned human primitive heart organoid model generated by pluripotent stem cell self-organization," Nature Communications, Nature, vol. 14(1), pages 1-22, 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:15:y:2024:i:1:d:10.1038_s41467-023-43502-w. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.