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

Pietro Mesirca (), Jean Chemin, Christian Barrère, Eleonora Torre, Laura Gallot, Arnaud Monteil, Isabelle Bidaud, Sylvie Diochot, Michel Lazdunski, Tuck Wah Soong, Stéphanie Barrère-Lemaire, Matteo E. Mangoni and Joël Nargeot ()
Additional contact information
Pietro Mesirca: Université de Montpellier, CNRS, INSERM
Jean Chemin: Université de Montpellier, CNRS, INSERM
Christian Barrère: Université de Montpellier, CNRS, INSERM
Eleonora Torre: Université de Montpellier, CNRS, INSERM
Laura Gallot: Université de Montpellier, CNRS, INSERM
Arnaud Monteil: Université de Montpellier, CNRS, INSERM
Isabelle Bidaud: Université de Montpellier, CNRS, INSERM
Sylvie Diochot: Laboratory of Excellence Ion Channels, Science & Therapeutics
Michel Lazdunski: Laboratory of Excellence Ion Channels, Science & Therapeutics
Tuck Wah Soong: National University of Singapore
Stéphanie Barrère-Lemaire: Université de Montpellier, CNRS, INSERM
Matteo E. Mangoni: Université de Montpellier, CNRS, INSERM
Joël Nargeot: Université de Montpellier, CNRS, INSERM

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-43502-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-43502-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-43502-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().