Wave sleep after anaesthesia. Etomidate also produced a large hypothermic effect in WT mice, which was reduced in the 2 N265S mice, and this effect may contribute to their rapid recovery from anaesthesia [30]. An equivalent mutation in the 3 subunit 3 N265M ; has also been generated and demonstrates that indeed the righting reflex after etomidate is profoundly affected in this mouse, as well as an abolition of the anaesthetic ability to prevent the paw withdrawal reflex [31]. These results together suggest that the 3 -containing receptors are the primary mediators of the anaesthetic effects of etomidate and this may well be generally applicable to other anaesthetics, whereas 2 , probably in combination with 1 , mediates the sedating effects of etomidate. The identification of residues, which affect the in vitro potentiation by volatile anaesthetics, suggest other mutants that might be useful in the investigation of these types of drugs. The ability to selectively affect function of these compounds suggests that we will soon learn a great deal more about the mechanism of action of anaesthetics and pathways which mediate the various effects produced by anaesthetics in vivo. As we learn more about the structure function of ligandgated ion channels at the molecular level, we can now apply this knowledge using transgenic technology to manipulate receptors in vivo. This provides us with useful tools to investigate the parts of the central nervous system, which mediate specific behaviours and identify the role of different ion channels in behaviour. Hopefully, this will open up a whole new arena of study in the field of ion channels and enable a much clearer understanding of how psychoactive drugs mediate their effects on the central nervous system.
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