Does the Residue at Position 356 Change Position Relative to the Conduction Pathway?
The results that mutation of Lys 356 largely restored TEA block in the absence of K+ could be explained by one of two possibilities. The first possibility, which we favor, is that the conformational change that occurs upon removal of K+ altered the position of Lys 356 relative to the conduction pathway. Movement of the positively charged lysine towards the center of the conduction pathway would interfere with the ability of TEA to enter the vestibule and/or bind to its binding site deeper in the pore. This effect might be especially profound if the lysines on each channel subunit moved relative to the central axis of the pore (see Panyi et al., 1995; Ogielska et al., 1995). Consequently, neutralization and/or reduction in the size of residue 356 would remove or reduce the interference between this residue and TEA binding, even if the mutation did not affect the K+-dependent conformational change. This possibility is directly supported by two observations. First, neutralization of this
