The GABAA receptor:An important target for the general anaesthetic etomidate

The general anaesthetic etomidate potently and selectively enhances the function of the GABAA receptor. Furthermore, etomidate is selective for GABAA receptors that incorporate a β2 or a β3 subunit, but is relatively ineffective at equivalent receptors containing the β1 subunit. This selectivity is governed by the nature of a single amino acid residue (asparagine, N for β2 and β3; serine, S for β1). Utilising this knowledge gene targeting was used to create a mouse in which the β2 subunit was engineered to be relatively insensitive to etomidate (β2N265S). In Purkinje neurones derived from such mice, the effects of etomidate on inhibitory synaptic transmission are greatly reduced. In complementary behavioural experiments, the mutation influences both the sedative and hypnotic actions of etomidate.