Interaction of propofol with recombinant AMPA receptors

The interaction of the anaestetic propofol with recombinant human AMPA-type glutamate receptor channels was investigated by a patch clamp study using fast agonist application techniques. Despite the marked effects of propofol on inhibitory synaptic transmission and voltage gated sodium channels, there is also evidence for a specific pharmacological action on AMPA receptors. In our study, we observed a deceleration of AMPA receptor channel desensitisation in the prolonged presence of glutamate and propofol that is likely to account for the enhancement of ion currents through AMPA receptor channels observed in previous studies. While there was an increase in the rate and extent of desensitisation at glutamate receptor 1, glutamate receptor 2, and glutamate receptor 3 AMPA receptors, no affection of current rise time, peak current amplitude, and deactivation properties was observed. Thus, our findings point to an isolated interaction with processes that control desensitisation of AMPA receptor channels rather than indicating an interaction with channel opening and closing processes due to agonist binding and unbinding. The pharmacological effect described resembles in part that of compounds like cyclothiazide and aniracetam which are known to interact with channel desensitisation.