Figure 4. The extent of channel block.

(a) Current-voltage (I-V) relationships for some M1 and M3 mutants, and the wild-type AChR. For clarity, only the I-V curve corresponding to the blocked open state (that is, the “sublevel”) is shown for each mutant. Position 244 in the β1 subunit aligns with position 247 in the δ subunit. The I-V curves corresponding to two M2 lysine mutants¹¹, δL265K (9′ position, on the pore-facing stripe of M2) and δQ267K (11′ position, on the backside of M2) are also shown. To facilitate the visual comparison of slopes, the individual I-V curves were voltage-shifted so that they all go through the origin. (b) Extent-of-channelblock values calculated from the slopes of I-V curves for positions in and flanking M1 (○) and M3 (•). For comparison, the values corresponding to δM2 (ref. 11) are also shown (•). M1 and M3 residue numbers (in red and black, respectively) correspond to those of the δ subunit. δM1-M2 loop and δM2 positions are denoted using the prime-numbering system (the-7′ position corresponds to δPro250 whereas 25′ corresponds to δThr281; we omit the -3′ position in the δ subunit). The unbroken line is a cubic-spline interpolation. Proposed membrane boundaries are tentative. The close correspondence between these open-state findings and the closed-state structural model (Fig. 2a; remember that the ionizable groups project radially several ångströms out from the Cδ trace) implies that only minor conformational changes are associated with gating of the AChR. For most positions, the horizontal error bars (standard errors) are smaller than the symbols. The lumen of the pore would be to the right of the plot.