Fig. 7: Macroscopic currents from the muscle AChR lacking allosteric loops C.

a Global superposition of atomic models of closed (unliganded; PDB ID: 7QKO¹¹) and open/desensitized (nicotine-bound; PDB ID: 7QL5¹¹) muscle-type AChR from Torpedo californica. The view is perpendicular to the membrane from the extracellular side. Loop-C atoms are colored blue (unliganded) or red (nicotine-bound); all other atoms are colored yellow (unliganded) or dark cyan (nicotine-bound). For the sake of clarity, neither the TMDs nor the molecules of bound nicotine are shown. Upon the binding of nicotine, the loops C of the α1 subunits rearrange much more extensively than those of the non-α-subunits. The sequences of the loops C of the adult mouse-muscle AChR’s β1, δ, and ε subunits are indicated (note the presence of an ε subunit in place of the γ subunit of Torpedo’s AChR). The molecular images were made with VMD⁵⁷ using cartoon representation. b, c Inward currents recorded from the indicated constructs in the whole-cell patch-clamp configuration in response to 20-ms (a) or 1-min (b) exposures to 100-μM ACh. For the wild-type mouse-muscle AChR (adult type), responses are shown as the mean (black solid line) ± 1 SD (gray error bars) of normalized responses recorded from different whole-cell experiments. Averaged wild-type data in (b) correspond to a total of 95 responses recorded from 12 different cells, and those in (c) correspond to a total of 10 individual responses recorded from 10 different cells. Each normalized trace shown for the loop-C-deleted mutants corresponds to a single response. In addition to introducing a proton-binding site, the reporter mutation (Leu-to-His at position 9ʹ of the M2 α-helix of the same subunit bearing the deletion of loop C) slows down the timecourses of deactivation (b) and entry into desensitization (c). The pipette potential was –60 mV. Black dashed lines denote the zero-current baseline. Source data are provided as a Source Data file.