Interactions of general anaesthetics with single acetylcholine receptor channels

We used single-channel recording techniques to study the effects of general anaesthetics on nicotinic acetylcholine receptor channels. Normally, these channels remain open for a few milliseconds. Anaesthetics induce three different patterns of channel activity. Ether causes the channel amplitude to be smaller and noisier than normal; isoflurane induces a flickery pattern in which openings occur in bursts of brief openings; propofol causes the channels to appear as isolated brief openings. These patterns can all be understood in terms of a model in which the anaesthetics bind directly to the channel protein and interrupt the flow of ions through the channel. The difference in pattern is determined by the duration of anaesthetic binding. Ether remains bound for the shortest period (< or = 0.01 ms), followed by isoflurane (0.5 ms) and propofol (> or = 2 ms). The anaesthetics may either be physically obstructing the pore of the channel or acting allosterically by inducing a new, non-conducting conformation of the channel.