Structures of A) voltage-gated sodium and B) voltage-gated Ca2+ channels. A) Secondary structure of the α-subunit of a voltage-gated Na+ channel showing four homologous domains, each of six transmembrane spanning segments (S1–S6). Pore loops link the S5 and S6, the positively charged S4 (blue) acts the voltage sensor and a short intracellular loop (red) linking domains III and IV acts as the inactivation gate. In a functional channel the domains are arranged so that the pore loops from each domain form the pore of the channel. Functional channels also require one or two modulatory β-subunits for activity. B) The α-sub-units of voltage-gated Ca2+ channels have a similar structure to that of the Na+ channels, and are the pore forming subunits of the channel. Functional channels however have a more complex structure an require the presence of β, γ and δ subunits.