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An Electrophysiological Study Of The Effects Of Propofol On Native Neuronal Ligand‐Gated Ion Channels
Author(s) -
Patten Debra,
Foxon Graham R,
Martin Keith F,
Halliwell Robert F
Publication year - 2001
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2001.03469.x
Subject(s) - strychnine , propofol , gabaa receptor , chemistry , glycine receptor , electrophysiology , vagus nerve , pharmacology , ion channel , receptor , endocrinology , medicine , neuroscience , glycine , biology , biochemistry , amino acid , stimulation
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‐HT 3 , 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 μ mol/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 μ mol/L had little or no effect on 5‐HT 3 , P2X or nACh receptor‐mediated responses in the vagus nerve but, at 100 μ mol/L, propofol inhibited these responses to approximately 50% of control. In the optic nerve, EC 20 GABA‐evoked responses were also potentiated by propofol (10 μ mol/L), while EC 20 glycine‐evoked responses were minimally enhanced. 4. Further investigations using cultured hippocampal neurons showed that submaximal (10 μ mol/L) GABA‐evoked currents were potentiated by propofol (1–10 μ mol/L), in a non‐voltage‐dependent manner, whereas submaximal (100 μ 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.