Selective blockade of Ca<inf>v</inf>1.2 (α1C) versus Ca<inf>v</inf>1.3 (α1D) L-type calcium channels by the black mamba toxin calciseptine
1
Issued Date
2024-12-01
Resource Type
eISSN
20411723
Scopus ID
2-s2.0-85181254808
Pubmed ID
38167790
Journal Title
Nature Communications
Volume
15
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Communications Vol.15 No.1 (2024)
Suggested Citation
Mesirca P., Chemin J., Barrère C., Torre E., Gallot L., Monteil A., Bidaud I., Diochot S., Lazdunski M., Soong T.W., Barrère-Lemaire S., Mangoni M.E., Nargeot J. Selective blockade of Ca<inf>v</inf>1.2 (α1C) versus Ca<inf>v</inf>1.3 (α1D) L-type calcium channels by the black mamba toxin calciseptine. Nature Communications Vol.15 No.1 (2024). doi:10.1038/s41467-023-43502-w Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/95756
Title
Selective blockade of Ca<inf>v</inf>1.2 (α1C) versus Ca<inf>v</inf>1.3 (α1D) L-type calcium channels by the black mamba toxin calciseptine
Corresponding Author(s)
Other Contributor(s)
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.