FIGURE 1.

Phe-1144 and Tyr-1152 reside in the pore segment of domain III. (A) Transmembrane folding model of the α₁ subunit of high voltage-gated Ca²⁺ channels. The α₁ subunit consists of four homologous domains, each consisting of six transmembrane segments (S1–S6). Four glutamate residues, one residing in each of the four loops connecting S5 and S6 in each domain, form the selectivity filter, or EEEE locus. The selectivity filter is thought to bind a single divalent cation with a high affinity or multiple divalent cations with a low affinity. (B) Alignment of the domain III pore segment from each of the 10 Ca²⁺ channel family members. All high voltage-activated Ca²⁺ channels have a glutamate residue at position 1145, and all low voltage-activated Ca²⁺ channels have an aspartate residue at this position (arrow). All L-type Ca²⁺ channels (Ca_V1.1–4) have a phenylalanine, all high voltage-activated non-L-type Ca²⁺ channels (Ca_V2.1–3) have a glycine, and all low voltage-activated T-type Ca²⁺ channels (Ca_V3.1–3) have a lysine residue at position 1144 (boxed). All L-type Ca²⁺ channels (Ca_V1.1–4) and T-type Ca²⁺ channels (Ca_V3.1–3) have a tyrosine residue at position 1152, whereas two of three non-L-type Ca²⁺ channels (Ca_V2.1–2) have a lysine residue at this position.