Davis, BM;
Brenton, J;
Davis, S;
Shamsher, E;
Sisa, C;
Grgic, L;
Cordeiro, MF;
(2017)
Assessing anesthetic activity through modulation of the membrane dipole potential.
Journal of Lipid Research
, 58
(10)
pp. 1962-1976.
10.1194/jlr.M073932.
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Abstract
There is great individual variation in response to general anaesthetics leading to difficulties in optimal dosing and sometimes even accidental awareness during general anaesthesia (AAGA). AAGA is a rare but potentially devastating complication affecting between 0.1% and 2% of patients undergoing surgery. The development of novel, personalised screening techniques to accurately predict a patient's response to GA and the risk of AAGA remains an unmet clinical need. In the present study we demonstrate the principle of using a fluorescent reporter of the membrane dipole potential, di-8-ANEPPs, as a novel method to monitor anaesthetic activity using a well-described inducer/non-inducer pair. The membrane dipole potential has previously been suggested to contribute a novel mechanism of anaesthetic action (Qin et al 1995). We show the fluorescence ratio of di-8-ANEPPs changed in response to physiological concentrations of the anaesthetic 1-chloro-1,2,2-trifluorocyclobutane (F3) but not the structurally similar non-inducer 1,2-dichlorohexafluorocyclobutane (F6) to artificial membranes and in vitro retinal cell systems. Modulation of the membrane dipole provides an explanation to overcome limitations associated with alternative membrane-mediated mechanisms of GA action. Furthermore, by combining this technique with non-invasive retinal imaging technologies, we propose this technique could provide a novel and non-invasive technique to monitor GA susceptibility and identify patients at risk of AAGA.
| Type: | Article |
|---|---|
| Title: | Assessing anesthetic activity through modulation of the membrane dipole potential |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1194/jlr.M073932 |
| Publisher version: | http://doi.org/10.1194/jlr.M073932 |
| Language: | English |
| Additional information: | Copyright © 2017, The American Society for Biochemistry and Molecular Biology. This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Accidental awareness during general anaesthesia, Cholesterol, Diagnostic tools, Eye/retina, Fluorescence, General Anaesthesia, Lipid rafts, Membrane dipole potential, Membranes/Model, di-8-ANEPPs |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1571608 |
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