| First Author | Mesirca P | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 54 |
| PubMed ID | 38167790 | Mgi Jnum | J:344285 |
| Mgi Id | MGI:7571965 | Doi | 10.1038/s41467-023-43502-w |
| Citation | Mesirca P, et al. (2024) Selective blockade of Ca(v)1.2 (alpha1C) versus Ca(v)1.3 (alpha1D) L-type calcium channels by the black mamba toxin calciseptine. Nat Commun 15(1):54 |
| abstractText | 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. |
