An electrophysiological study of the effects of propofol on native neuronal ligand-gated ion channels

1. Pharmacological evidence suggests that some of the clinical actions of p ropofol may be mediated, at least in part, by positive modulation of the GA BA(A) receptor chloride channel. The effect of propofol at other native neu ronal ligand-gated ion channels is unclear. 2. To gain some insight into the effects of propofol at a range of native n euronal receptors, the present study has used an extracellular recording te chnique and determined its effects at GABA(A), 5-HT3, P2X and nicotinic ace tylcholine (nACh) receptors of the rat isolated vagus nerve and the GABA(A) and strychnine-sensitive glycine receptor of the rat isolated optic nerve. In addition, we have used patch-clamp recording techniques to further inve stigate the effects of propofol at the GABA(A) and strychnine-sensitive gly cine receptors in rat cultured hippocampal neurons. 3. Propofol (0.3-100 mu mol/L) concentration-dependently potentiated submax imal GABA-evoked responses in the vagus nerve and shifted the GABA concentr ation-response curve to the left. In contrast, propofol at concentrations r anging from 1 to 10 mu mol/L had little or no effect on 5-HT3, P2X or nACh receptor-mediated responses in the vagus nerve but, at 100 mu mol/L, propof ol inhibited these responses to approximately 50% of control. In the optic nerve, EC20 GABA-evoked responses were also potentiated by propofol (10 mu mol/L), while EC20 glycine-evoked responses were minimally enhanced. 4. Further investigations using cultured hippocampal neurons showed that su bmaximal (10 mu mol/L) GABA-evoked currents were potentiated by propofol (1 -10 mu mol/L), in a non-voltage-dependent manner, whereas submaximal (100 m u mol/L) glycine-evoked currents were unaffected. 5. These data suggest that propofol, at therapeutic concentrations, exerts its principle pharmacological actions at GABA(A) receptors with relatively little effect at other neuronal ligand-gated ion channels.