Introduction: Selective blockers are important tools for identifying the physiological role of ion channels isoforms. L-type calcium channels are high voltage activated channels sensitive to dihydropyridine (DHP). Two distinct isoforms (1C/Cav1.2 and 1D/Cav1.3) mediate calcium entry into cardiac cells to trigger contraction or contribute to heart rate generation. Many classes of drugs have been shown to target L-type calcium channels but poor selectivity has been reported between Cav1.2 and Cav1.3. Objective: Our goal is to look for an animal toxin able to discriminate between these two L-type calcium channel isoforms. We focused on calciseptine, a snake toxin purified from mamba venom which decreases, via Cav1.2 inhibition, vascular and cardiac contraction without affecting heart rate (De Weille et al, 2001). Methods: We compared the effect of calciseptine and of a classical DHP on the contraction amplitude and heart rate in Langendorf perfused hearts from wild-type mice and mice carrying Cav1.2 channels insensitive to DHP. Results: Calciseptine 100 nM strongly decreased the amplitude of contractions by 82%. Increasing the concentration up to 1 µM further reduced the contraction while no modification of the heart rate was noticed. The frequency of spontaneous AP recorded from sinus node using the patch clamp technique was also unaffected by 100nM calciseptine. (216±20 bpm ctrl vs 212±22 bpm calciseptine). On the other hand, 3 µM nifedipine, which blocks both Cav1.2 and Cav1.3 channels decreased contraction and heart rate in isolated mouse heart, induced arrhythmias and strongly reduced AP frequency in isolated sinus node cells (193±10 bpm ctrl vs 48±9 bpm nifedipine). Conclusions: These preliminary data suggest that calciseptine may act as a specific blocker of Cav1.2 versus Cav1.3, a result to be confirmed by direct exploration of the effect of calciseptine on native ventricular and SAN cells calcium currents or on recombinant Cav1.2 and Cav1.3 currents.