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

Lookup NU author(s): Dr Debra Patten

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Abstract

ABSTRACT SUMMARY 1. Pharmacological evidence suggests that some of the clinical actions of propofol may be mediated, at least in part, by positive modulation of the GABA_A 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 GABA_A, 5-HT₃, P2X and nicotinic acetylcholine (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 investigate the effects of propofol at the GABA_A 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 GABA_A receptors with relatively little effect at other neuronal ligand-gated ion channels.

Publication metadata

Author(s): Patten D, Foxon GR, Martin KF, Halliwell RF

Publication type: Article

Publication status: Published

Journal: Clinical and Experimental Pharmacology and Physiology

Year: 2001

Volume: 28

Issue: 5-6

Pages: 451-458

Print publication date: 01/05/2001

Online publication date: 30/01/2002

ISSN (print): 0305-1870

ISSN (electronic): 1440-1681

Publisher: John Wiley & Sons, Inc.

URL: https://doi.org/10.1046/j.1440-1681.2001.03469.x

DOI: 10.1046/j.1440-1681.2001.03469.x

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