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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
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    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.
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