Ion flow gating by the acetylcholine system: kinetics of isolated receptor and esterase and of receptor-mediated ion flux.

1. Basic features of the elementary bioelectric signals such as miniature-endplate-potentials are molecularly interpreted on the basis of relaxation kinetic data of isolated acetylcholine receptor and acetylcholinesterase. Electrophysiological and molecular data suggest an essentially sequential processing of acetylcholine by receptor and esterase. 2. Flux measurements with sealed biomembrane fragments containing acetylcholine receptor show that the ion-transporting conformation of the receptor-channel is a short-lived metastable state. In the presence of neuroactivators the receptors inactivate. The description of the flux-inactivation requires a cyclic reaction scheme similar to the desensitization scheme of KATZ and THESLEFF (1957). 3. The recently introduced concept of integrated flux rate coefficients permits us to derive gating mechanisms from flux data under well-defined experimental conditions: sealed biomembrane vesicles, activator concentration, type of transported ion. 4. With respect to activation and inactivation and the metastability of the ion-conducting conformation, there are fundamental similarities between the axonal Na+ ion channel and the acetylcholine receptor-channel.