Most neurotransmitter receptors belong to either the pentameric nicotinoid receptor family or the tetrameric glutamatergic receptor family. The muscle nicotinic acetylcholine receptor (AChR), the prototype of the nicotinoid receptor family, gates by switching between a closed configuration (in which ion permeation is forbidden) and an open configuration (which allows ions to pass through). Rate-equilibrium linear free energy relationship analysis has allowed us to explore the transition state that links these two stable conformations. A series of point mutations were made to individual AChR residues, and the ensuing changes in the rate constants of channel opening and closing for the fully liganded receptor were determined. These experiments suggest that gating occurs approximately as a reversible, solitary conformational wave that propagates between the neurotransmitter binding site and the membrane domain, along the long axis of the receptor. A detailed knowledge of the gating mechanism can serve as a basis for understanding the shape of the postsynaptic ion current and for the differences in synaptic responses among different ligand-gated channels.