Calciseptine is a peptide toxin originally isolated from black mamba (Dendroaspis polylepsis) venom (1, 2). A three-finger toxin, calciseptine consists of 60 amino acids with 4 disulfide bridges (2). It is a specific L-type Ca_V channel blocker selective for Ca_V1.2 (3). Calciseptine binds to the shoulder of the Ca_V1.2 pore domain and traps the channel in a non-conductive conformation (4).

Calciseptine blocks spontaneous or K⁺-induced contraction of cardiac and smooth muscle cells (2). However, in skeletal muscle, it increases L-type currents, modulating Ca²⁺ permeation (5). Using a patch clamp, calciseptine was shown to specifically block L-type Ca_V channel currents in neuronal cells in culture, with IC₅₀ values of 15-500 nM (2). It was also shown to reduce the open probability and availability of the L-type channel in guinea pig portal vein smooth muscle cells, using outside-out patch clamping (6).

Ca_V1.2 is one of 10 voltage-gated calcium channels (VGCCs), which are divided into three families based on the pore-forming α1 subunit (7); they were originally divided based on activation voltage current (8). Encoded by the CACNA1C gene, Ca_V1.2 consists of the three subunits α₁, a₂δ, and β. This channel is expressed by smooth and cardiac muscle, pancreas, neurons, and fibroblasts. It is involved in central nervous system function and neuroendocrine regulation, cardiac and smooth muscle contractibility, and multiple other physiological processes (9).