Halogenated general anesthetics in visual photoreceptor membranes as examined by static and dynamic properties of rhodopsin

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Abstract
The visual pigment rhodopsin was used as an intrinsic probe to measure the effect of incorporation of enflurane into bovine rod outer segment disk membranes. At moderately low enflurane concentration, we find that, while extrinsic probes show little membrane perturbation, rhodopsin may experience large changes with respect to the native lipid–protein interactions which modulate some of its properties. Enflurane induces a small blue shift in the pigment λmax and a strong inhomogeneity in its photochemical behavior. As a function of enflurane concentration, there appears to be an increasing population of rhodopsin molecules for which the metarhodopsin I → II transition is blocked, while it is accelerated in the remaining population. Under these conditions, electrophoresis and partial membrane solubilization indicate that an increasing amount of rhodopsin does not behave like a free monomeric species. These results are all consistent with a reduction of the membrane order accompanied by lateral aggregation of rhodopsin in the presence of enflurane. By comparison with the perturbation probed by a spin label, the large molecular environment change experienced by the rhodopsin molecule suggests that enflurane may concentrate at the lipid-protein interface.Key words: anesthetics, flash photolysis, lateral aggregation, rhodopsin, visual membranes.

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