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J. Gen. Physiol.,
Volume 112, Number 2, August 1, 1998 181-197
From the Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York 14214
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.
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