Desensitization of mouse nicotinic acetylcholine receptor channels. A two-gate mechanism

Anthony Auerbach, Gustav Akk

Research output: Contribution to journalArticlepeer-review

142 Scopus citations

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 tile nature of the agonist, the membrane potential, the species of permeant cation, channel block by ACh, the subunit composition (ε or γ), 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.

Original languageEnglish
Pages (from-to)181-197
Number of pages17
JournalJournal of General Physiology
Volume112
Issue number2
DOIs
StatePublished - Aug 1998

Keywords

  • Electrophysiology
  • Kinetics
  • Single-channel

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