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

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 Ca v 1.2 and Ca v 1.3 that are concomitan...

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Published in:Nature communications 2024-01, Vol.15 (1), p.54-54, Article 54
Main Authors: Mesirca, Pietro, Chemin, Jean, Barrère, Christian, Torre, Eleonora, Gallot, Laura, Monteil, Arnaud, Bidaud, Isabelle, Diochot, Sylvie, Lazdunski, Michel, Soong, Tuck Wah, Barrère-Lemaire, Stéphanie, Mangoni, Matteo E., Nargeot, Joël
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Language:English
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Summary: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 Ca v 1.2 and Ca v 1.3 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 Ca v 1.2 -mediated L-type calcium currents (I CaL ) at concentrations leaving Ca v 1.3-mediated I CaL unaffected in both native cardiac myocytes and HEK-293T cells expressing recombinant Ca v 1.2 and Ca v 1.3 channels. Functionally, calciseptine potently inhibits cardiac contraction without altering the pacemaker activity in sino-atrial node cells, underscoring differential roles of Ca v 1.2− and Ca v 1.3 in cardiac contractility and automaticity. In summary, calciseptine is a selective L-type Ca v 1.2 Ca 2+ channel blocker and should be a valuable tool to dissect the role of these L-channel isoforms. L-type voltage-gated calcium channels are involved in multiple physiological functions. Here the authors identify calciseptine, a toxin purified from black mamba venom, as a selective inhibitor of Ca v 1.2 L-type Ca 2+ channels.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-43502-w