Fluctuations in the microsecond time range of the current through single acetylcholine receptor ion channels

Acetylcholine-like drugs cause ion channels in the skeletal muscle endplate to open briefly1, producing, at random intervals, rectangular pulses of current with constant amplitude but random duration, that can be recorded by the patch clamp method2,3. However, even when the agonist concentration is so low that channel activations are very well separated, we have observed, with high resolution methods4, that openings may be interrupted by shut periods (gaps) so brief that they are very unlikely to arise from two independent channel activations. This sort of behaviour has been predicted on the basis that two or more openings might occur during the time for which the receptor remains occupied by agonist5,6. If this were correct, important new information about agonist activation of ion channels could be obtained from measurements of the gaps between openings. However, short gaps could arise in other ways: for example from brief blockage of the ion channel7, perhaps by the agonist itself. We now present results obtained with the acetylcholine-like agonist, suberyldicholine (SubCh, 20–100 nM), which suggest that the brief gaps do not result from ion channel block by the agonist itself, but which are consistent with a mechanism in which the channel opens and closes several times during a single agonist receptor occupancy. We have also observed that the number of short (