(A) Transmembrane view of a single subunit of CaV1.1 (PDB accession 3JBR) to illustrate the architecture of the pore domain (P1, P2, S5, and S6), voltage-sensing domain (S1–S4), and linker regions common to voltage-gated sodium and calcium channels. The N-terminus is colored blue, and the C-terminus is colored red in ribbon representation. (B) Top view of CaV1.1 colored to highlight the heterotetrameric arrangement of the voltage-sensing and pore domains, with the ion-conducting pore in the center. (C) Transmembrane view of CaV1.1 highlighting the C-terminal domain important for ion channel regulation, as well as a transmembrane fenestration important for local anesthetic ingress. Kevin R. DeMarco.