Binding of Ala-scanning analogs of ω-conotoxin MVIIC to N- and P/Q-type calcium channels

ω-Conotoxin MVIIC binds to P/Q-type calcium channels with high affinity and N-type channels with low affinity. To reveal the residues essential for subtype selectivity, we synthesized Ala-scanning analogs of MVIIC. Binding assays using rat cerebellar P2 membranes suggested that Thr11, Tyr13 and Lys2 are essential for binding to both N- and P/Q-type channels, whereas Lys4 and Arg22 are important for binding to P/Q-type channels. These results suggest that MVIIC interacts with P/Q-type channels via a large surface, in good agreement with previous observations using chimeric analogs.