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Papers of the Week

Papers: 30 Dec 2023 - 5 Jan 2024

2024 Jan 02

Nat Commun




Selective blockade of Ca1.2 (α1C) versus Ca1.3 (α1D) L-type calcium channels by the black mamba toxin calciseptine.


Mesirca P, Chemin J, Barrère C, Torre E, Gallot L, Monteil A, Bidaud I, Diochot S, Lazdunski M, Soong TW, Barrère-Lemaire S, Mangoni ME, Nargeot J


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 Ca1.2 and Ca1.3 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 Ca1.2 -mediated L-type calcium currents (I) at concentrations leaving Ca1.3-mediated I unaffected in both native cardiac myocytes and HEK-293T cells expressing recombinant Ca1.2 and Ca1.3 channels. Functionally, calciseptine potently inhibits cardiac contraction without altering the pacemaker activity in sino-atrial node cells, underscoring differential roles of Ca1.2- and Ca1.3 in cardiac contractility and automaticity. In summary, calciseptine is a selective L-type Ca1.2 Ca channel blocker and should be a valuable tool to dissect the role of these L-channel isoforms.