Thermal behavior of a lipid-protein membrane model and the effects produced by anesthetics and neurotransmitters

Despite decades of intense research to understand the phenomenon of anesthesia and its membrane-related changes in neural transmission, where lipids and proteins have been proposed as primary targets of anesthetics, the involved action mechanisms remain unclear. Based on the overall agreement that anesthetics and neurotransmitters induce particular modifications in the plasma membrane of neurons, triggering specific responses and changes in their energetic states, we present here a thermal study to investigate membrane effects in a lipid-protein model made of 1,2-dimyristoyl-sn-glycero-3-phosphocholine and albumin from chicken egg white under the influence of neurotransmitters and anesthetics. First, we observe how ovalbumin, ovotransferrin, and lysozyme (main albumin constituents from chicken egg white) interact with the lipid membrane enhancing their lipophilic character while exposing their hydrophobic domains. This produces a lipid separation and a more ordered hybrid lipid-protein assembly. Second, we measured the thermotropic changes of this assembly induced by acetylcholine, γ-aminobutiric acid, tetracaine, and pentobarbital. Although the protein in our study is not a receptor, our results are striking, for they give evidence of the great importance of non-specific interactions in the anesthesia mechanism. [Display omitted] •Lipid/protein interactions drive the incorporation of soluble globular proteins in multilamellar liposomes.•The gel/liquid transition of DMPC membranes shifts to a higher temperature upon the insertion of the OVA protein.•Pure DMPC membranes are calorimetrically unaffected by acetylcholine and GABA, but DMPC-OVA membranes interact with these neurotransmitters.