Propofol, a general anesthetic, promotes the formation of fluid phase domains in model membranes.
The molecular site of anesthetic action remains an area of intense research interest. It is not clear whether general anesthetics act through direct binding to proteins or by perturbing the membrane properties of excitable tissues. Several studies indicate that anesthetics affect the properties of either membrane lipids or proteins. However, gaps remain in our understanding of the molecular mechanism of anesthetic action. Recent developments in membrane biology have led to the concept of small-scale domain structures in lipid and lipid--protein coupled systems. The role of such domain structures in anesthetic action has not been studied in detail. In the present study, we investigated the effect of anesthetics on lipid domain structures in model membranes using the fluorescent spectral properties of Laurdan (6-dodecanoyl-2-dimethylamino naphthalene). Propofol, a general anesthetic, promoted the formation of fluid domains in model membranes of dipalmitoyl phosphatidyl choline (DPPC) or mixtures of lipids of varying acyl chains (DPPC:DMPC dimyristoyl phosphatidyl choline 1:1). The estimated size of these domains is 20--50 A. Based on these studies, we speculate that the mechanism of anesthetic action may involve effects on protein--lipid coupled systems through alterations in small-scale lipid domain structures.
Balasubramanian
Sathyamangalam V
SV
Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, 539 Cooke Hall, Amherst, NY 14260-1200, USA. svb@acsu.buffalo.edu
Campbell
Robert B
RB
Straubinger
Robert M
RM
D015060:1,2-Dipalmitoylphosphatidylcholine; D015081:2-Naphthylamine / Q000031:analogs & derivatives*; D018681:Anesthetics, General / Q000494:pharmacology*; D004134:Dimyristoylphosphatidylcholine; D005456:Fluorescent Dyes; D007848:Laurates; D008081:Liposomes; D008560:Membrane Fluidity / Q000187:drug effects*; D021962:Membrane Microdomains; D008567:Membranes, Artificial; D015742:Propofol / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence
D018681:Anesthetics, General; D005456:Fluorescent Dyes; D007848:Laurates; D008081:Liposomes; D008567:Membranes, Artificial; D015060:1,2-Dipalmitoylphosphatidylcholine; D015081:2-Naphthylamine; D004134:Dimyristoylphosphatidylcholine; C065580:laurdan; D015742:Propofol