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.Mahidol University2024-02-082024-02-082024-12-01Nature Communications Vol.15 No.1 (2024)https://repository.li.mahidol.ac.th/handle/123456789/95756L-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.ChemistryBiochemistry, Genetics and Molecular BiologyPhysics and AstronomyArticleSCOPUS10.1038/s41467-023-43502-w2-s2.0-851812548082041172338167790