INTERACTIONS OF GENERAL-ANESTHETICS WITH SINGLE ACETYLCHOLINE-RECEPTOR CHANNELS

We used single-channel recording techniques to study the effects of ge neral anaesthetics on nicotinic acetylcholine receptor channels. Norma lly, these channels remain open for a few milliseconds. Anaesthetics i nduce three different patterns of channel activity. Ether causes the c hannel amplitude to be smaller and noisier than normal; isoflurane ind uces a flickery pattern in which openings occur in bursts of brief ope nings; propofol causes the channels to appear as isolated brief openin gs. These patterns can all be understood in terms of a model in which the anaesthetics bind directly to the channel protein and interrupt th e flow of ions through the channel. The difference in pattern is deter mined by the duration of anaesthetic binding. Ether remains bound for the shortest period (less-than-or-equal-to 0.01 ms), followed by isofl urane (0.5 ms) and propofol (greater-than-or-equal-to 2 ms). The anaes thetics may either be physically obstructing the pore of the channel o r acting allosterically by inducing a new, non-conducting conformation of the channel.