D Patten
An electrophysiological study of the effects of propofol on native neuronal ligand-gated ion channels
Patten, D; Foxon, GR; Martin, KF; Halliwell, RF
Authors
GR Foxon
KF Martin
RF Halliwell
Abstract
1. Pharmacological evidence suggests that some of the clinical actions of propofol may be mediated, at least in part, by positive modulation of the GABAA receptor chloride channel. The effect of propofol at other native neuronal ligand-gated ion channels is unclear. 2. To gain some insight into the effects of propofol at a range of native neuronal receptors, the present study has used an extracellular recording technique and determined its effects at GABAA, 5-HT3, P2X and nicotinic acetylcholine (nACh) receptors of the rat isolated vagus nerve and the GABAA and strychnine-sensitive glycine receptor of the rat isolated optic nerve. In addition, we have used patch-clamp recording techniques to further investigate the effects of propofol at the GABAA and strychnine-sensitive glycine receptors in rat cultured hippocampal neurons. 3. Propofol (0.3–100 μmol/L) concentration-dependently potentiated submaximal GABA-evoked responses in the vagus nerve and shifted the GABA concentration–response curve to the left. In contrast, propofol at concentrations ranging from 1 to 10 μmol/L had little or no effect on 5-HT3, P2X or nACh receptor-mediated responses in the vagus nerve but, at 100 μmol/L, propofol inhibited these responses to approximately 50% of control. In the optic nerve, EC20 GABA-evoked responses were also potentiated by propofol (10 μmol/L), while EC20 glycine-evoked responses were minimally enhanced. 4. Further investigations using cultured hippocampal neurons showed that submaximal (10 μmol/L) GABA-evoked currents were potentiated by propofol (1–10 μmol/L), in a non-voltage-dependent manner, whereas submaximal (100 μmol/L) glycine-evoked currents were unaffected. 5. These data suggest that propofol, at therapeutic concentrations, exerts its principle pharmacological actions at GABAA receptors with relatively little effect at other neuronal ligand-gated ion channels.
Citation
Patten, D., Foxon, G., Martin, K., & Halliwell, R. (2001). An electrophysiological study of the effects of propofol on native neuronal ligand-gated ion channels. Clinical and Experimental Pharmacology and Physiology, 28(5-6), 451-458. https://doi.org/10.1046/j.1440-1681.2001.03469.x
Journal Article Type | Article |
---|---|
Publication Date | May 1, 2001 |
Deposit Date | May 10, 2007 |
Journal | Clinical and Experimental Pharmacology and Physiology |
Print ISSN | 0305-1870 |
Electronic ISSN | 1440-1681 |
Publisher | Wiley |
Peer Reviewed | Peer Reviewed |
Volume | 28 |
Issue | 5-6 |
Pages | 451-458 |
DOI | https://doi.org/10.1046/j.1440-1681.2001.03469.x |
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