This animation, which depicts a speculative view of nicotinic acetylcholine receptor gating, was adapted by Cameron Slayden from an animation by R. Foxenberg. The structures are from acetylcholine binding protein in the extracellular domain (α subunit, aqua; ε subunit, gold) and represent the M4 (straight) and M2 (kinked) segments of the acetylcholine receptor α subunit (left) and δ subunit (right) in the membrane domain (red). The kink in M2 is based on the results of Unwin. The small circles represent residues whose φ values have been probed by mutations. The moving elements switch from closed (gray) to open (yellow) at times set by the φ value for that position. The duration of the overall closed to open reaction is not known but may be ≤1 μs. Some residues do not change color: gray, sites where mutations do not change the gating equilibrium constant; blue, sites where mutations result in no expression or no gating; brown: sites where mutations have catalytic effects that prevent the estimation of a φ value. The φ values of the δ-subunit M2 domain have been determined but those of the α-subunit M2 domain are, at this juncture, speculative. The orientation is such that the extracellular side is above the membrane and the intracellular side is below the membrane.