Acetylcholine Receptors, Between Closed and Open

Summary

Muscle acetylcholine receptors switch between conformations that either allow (‘open’) or prohibit (‘closed’) ion permeation. We probed the dynamics of this structural transition using linear free-energy relationships. Specific regions of the protein were perturbed (mutations, voltage or agonists) and the opening and closing rate constants were estimated from single-channel currents. Usually, a log–log plot of rate constant versus equilibrium constant was linear, with the slope indicating the sensitivity of the transition state to the perturbation as being between that of the open and closed conformation. The spatial gradient in this slope, from open-like at the transmitter binding sites to closed-like at the middle of the membrane, suggests that gating is a wave that propagates between the binding sites and the membrane domain.