Calciseptine TFA, a polypeptide found in black mamba venom, is a selcetive Cav1.2 L-type calcium channel inhibitor with an IC50 of 92 nM. Calciseptine TFA binds to the pore domain shoulder at repeats III and IV of Cav1.2, stabilizing an inactivated conformation. Calciseptine TFA exhibits negative inotropic and negative relaxant effects on mice, and does not affect heart rate or the action potential of sinoatrial node pacemaker cells. Calciseptine TFA can be used for the research of cardiovascular diseases [1] [2].
In Vivo, Calciseptine (100 nM; perfusion; continuous; 7 minutes) TFA inhibits contraction and spares automaticity of Langendorff perfused hearts[1].
In Vitro, Calciseptine (100 nM-1 μM) TFA potently inhibits recombinant Cav1.2-mediated L-type Ca2+ currents in HEK-293T cells with an IC50 of 92 ± 18 nM, while having no significant effect on recombinant Cav1.342α- or Cav1.342-mediated currents at concentrations up to 1 μM[1]. Calciseptine (40-1000 nM) TFA inhibits Cav1.2 channel activity in HEK293T cells and 0.2 μM reducing peak Cav1.2 current by more than half[2]. Calciseptine TFA requires Cav1.2 residues Asp1117, Val1501, Asn1113, and Ala1123 for specific blockage of Cav1.2, as mutation of these residues reduces sensitivity Calciseptine[2].
References:
[1]. Mesirca P, et al. Selective blockade of Cav1.2 (α1C) versus Cav1.3 (α1D) L-type calcium channels by the black mamba toxin calciseptine. Nat Commun. 2024 Jan 2;15(1):54.
[2]. Gao S, et al. Structural basis for human Ca v 1.2 inhibition by multiple drugs and the neurotoxin calciseptine. Cell. 2023;186(24):5363-5374.e16.
In Vivo, Calciseptine (100 nM; perfusion; continuous; 7 minutes) TFA inhibits contraction and spares automaticity of Langendorff perfused hearts[1].
In Vitro, Calciseptine (100 nM-1 μM) TFA potently inhibits recombinant Cav1.2-mediated L-type Ca2+ currents in HEK-293T cells with an IC50 of 92 ± 18 nM, while having no significant effect on recombinant Cav1.342α- or Cav1.342-mediated currents at concentrations up to 1 μM[1]. Calciseptine (40-1000 nM) TFA inhibits Cav1.2 channel activity in HEK293T cells and 0.2 μM reducing peak Cav1.2 current by more than half[2]. Calciseptine TFA requires Cav1.2 residues Asp1117, Val1501, Asn1113, and Ala1123 for specific blockage of Cav1.2, as mutation of these residues reduces sensitivity Calciseptine[2].
References:
[1]. Mesirca P, et al. Selective blockade of Cav1.2 (α1C) versus Cav1.3 (α1D) L-type calcium channels by the black mamba toxin calciseptine. Nat Commun. 2024 Jan 2;15(1):54.
[2]. Gao S, et al. Structural basis for human Ca v 1.2 inhibition by multiple drugs and the neurotoxin calciseptine. Cell. 2023;186(24):5363-5374.e16.