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A Two-Gate Mechanism
ABSTRACT
The rate constants of acetylcholine receptor channels (AChR) desensitization and recovery were estimated from the durations and frequencies of clusters of single-channel currents. Diliganded-open AChR desensitize much faster than either unliganded- or diliganded-closed AChR, which indicates that the desensitization rate constant depends on the status of the activation gate rather than the occupancy of the transmitter binding sites. The desensitization rate constant does not change with the nature of the agonist, the membrane potential, the species of permeant cation, channel block by ACh, the subunit composition (
or 
), or several mutations that are near the transmitter binding sites. The results are discussed in terms of cyclic models of AChR activation, desensitization, and recovery. In particular, a mechanism by which activation and desensitization are mediated by two distinct, but interrelated, gates in the ion permeation pathway is proposed.
Key Words: single-channel • kinetics • electrophysiology
This paper is dedicated to Professor Bernard Katz. We thank J. Dilger for providing the experimental results shown in Fig. 9, and M. Zhou for the
N217K and G153S results shown in Table II. Claudio Grosman derived the cluster duration correction. We thank C. Grosman, D. Machonochie, S. Sine, C. Lingle, and F. Qin for comments on the manuscript. We thank Karen Lau for technical assistance.
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