Résumé
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$1.2 -mediated L-type calcium currents (ICaL) at concentrations leaving Ca$_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 Ca2+ channel blocker and should be a valuable tool to dissect the role of these L-channel isoforms.