Figure 11. Hypothetical model for the mechanism of action of PCCP⁻.

Mutation of residues α₁V256 and α₁T261 to cysteine alters strongly the apparent affinity for channel inhibition by PCCP⁻. The fact that MTSET⁺ can only react with cysteines introduced in M2 in the presence of GABA indicates that GABA widens the pore. For the mutations α₁V256C and α₁T260C the affinity for PCCP⁻ is strongly increased after MTSET⁺ treatment. MTSET⁺ reaction is prevented by PCCP⁻. This together implies these residues in PCCP⁻ binding. Introduction of two positive charges by reaction with MTSET⁺ further up in the channel leads to additional binding sites for PCCP⁻.