Schematic illustration of the Ca_V1.2 α subunit emphasizing the spatial relationship of key regulatory sites located at the proximal C terminus. Ca_V1.2, α subunit composed of the N terminus, the four homologous domains with six transmembrane segments, and a reentrant pore loop in each (I–IV), and the C-terminus. The arrows point to the conformational interactions between the distal C terminus (DCT; red arrow) and the IQ motif (Ca²⁺/CaM) (orange arrow) independently converging on the EF-hand motif (Mg²⁺), which subsequently may modify the conformation of domain IV S6 segment of the Ca_V1.2 α subunit to alter channel-gating properties. The scissors illustrate the site of proteolytic cleavage. CaM, calmodulin.