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Fluorescence anisotropy of diphenylhexatriene and its cationic Trimethylamino derivative in liquid dipalmitoylphosphatidylcholine liposomes: opposing responses to isoflurane

DOI: 10.1186/2046-1682-5-5

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Abstract:

In liquid crystalline dipalmitoylphosphatidylcholine liposomes, isoflurane (7-25 mM in the bath) increases trimethylammonium-diphenylhexatriene fluorescence anisotropy by ~0.02 units and decreases diphenylhexatriene anisotropy by the same amount.The anisotropy data suggest that isoflurane decreases non-axial dye mobility in the headgroup region, while increasing it in the tail region. We propose that these results reflect changes in the lateral pressure profile of the membrane.Inhaled volatile general anesthetics block pain, memory, consciousness, and movement by inhibiting excitatory channels and activating inhibitory channels [1] with weak potency (generally > 100 μM inhibitory constant). Debate continues over whether the mechanism is lipid mediated [2,3] or involves direct binding to ion channels [4], and obviously could involve both. In molecular dynamics simulations, lateral pressures have been found to be positive in the head and tail regions and very negative at the level of the glycerol ester oxygens [5]. Insertion of surfactants, such as volatile anesthetics, could influence these pressures [2] by increasing area per headgroup, thinning the membrane to maintain molecular volume, and increasing the lateral pressure in the headgroup and glycerol regions while reducing it in the tail region. Indeed, ethanol was found in simulations to increase the lateral pressure in the glycerol region [6,7]. Halothane was found in simulations to accumulate below the interface [8]. Such changes may differentially affect protein cross-section during function [9], and have been suggested to play a role in modulation of ion channels [10-12].Support for the theory that general anesthetics affect the lateral pressure profile has been provided by the observation that diphenylhexatriene (DPH) and trimethylammonium-DPH (TMA-DPH) show decreased fluorescence anisotropy with increased volatile anesthetic addition in red blood cell ghosts [13]. This begs interpretation from molecular dyn

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