Figure 1.

Schematic representation of voltage-gated Ca²⁺ channel topology and subunit composition. (A) Topology of the pore forming α₁ subunit. There are four homologous repeats (domain I through domain IV) each with six transmembrane spanning α-helices (S1–S6) (blue or orange cylinders) and a ‘P-loop’ between S5 and S6. The pore domain (orange) comprises the S5–S6 and P-loop segments, and the voltage-sensor domain (blue) consists of the S1–S4 segments (in particular S4 that has multiple charged residues). The intracellular N- and C-termini and the cytoplasmic loops connecting domains I–IV are all important for interaction with other proteins including the auxiliary β subunit of the channel that binds to the AID on the I–II linker, synaptic proteins that interact at the “synprint site”, and G protein βγ heterodimers (Gβγ) that interact at three sites on the N-terminus, I–II linker and C-terminus (see text for more details). (B) Representation showing the 3D topology with the intracellular β subunit that interacts through its GK domain with the AID on the I–II linker of the α₁ subunit. The α₂δ subunit is largely extracellular and likely GPI-anchored to the plasma membrane.