Figure 1.

Localization of the DHP binding site in l-type channels. (A) Studies utilizing DHP photoaffinity labels and site-directed antibodies (28, 29) identified transmembrane segments IIIS6 and IVS6 of l-type Ca²⁺ channels as components of the DHP binding site. Boundaries of the labeled peptides (shaded cylinders and thick lines) are shown as amino acid sequence numbers from α_1S (6). Subsequent studies utilizing chimeric Ca²⁺ channels further demonstrated the role of IIIS6 and IVS6 as well as transmembrane domain IIIS5 in DHP moduation of l-type channels (32–34). (B) Structure of α_1A/DHPS. Studies of single amino acid substitutions in l-type channels revealed nine l-type-specific (black circles with white letters) and five conserved (white circles with black lower case letters) amino acid residues to be critical for DHP binding and block of l-type channels (34–38). The nine l-type-specific amino acid residues critical for DHP action were inserted into the DHP-insensitive α_1A subunit amino acid sequence (14) (white circles with black letters) to a construct a mutant α_1A subunit that is modulated by DHPs (α_1A/DHPS).