Wednesday, 22 June 2011

Liquid Courage

So my previous post I talked about drinking alcohol a.k.a liquid courage (this could not be more true in Finland since people are quite shy but after a few out!!).  Even though alcohol has so many physiological, sociological and other effects and is quite a clear anesthetic there are still a lot of undetermined things about ethanol.  It is understood that it can easily interdigitate due to its size into the cell membrane and change the membrane's physical properties.  This could change the phase transition, the fluidity, the lipid movement, dipole potential and even affect the amount of polyunsaturated lipids (REF) at the synaptic membrane (this is over chronic ethanol ingestion).  All these effects would affect the proteins where these lipids are embedded giving people slower reaction times. 

One assay on how understand the effects of alcohol on the membrane is to use monolayer films with compression isotherms.  A single layer film is deposited on a subphase of a trough of a known area (usually water) and the area per molecule can be calculated (this was first performed by Benjamin Franklin).  Then two teflon barriers on opposite sides of the trough slowly compress changing the trough area.  The area per molecule can be calculated.  The surface tension and other parameters like surface potential can be recorded if available.  Usually the surface tension is recorded to give a graph of surface tension vs. area per molecule.   What happens when ethanol is added to this type of system?

A pretty comprehensive review of alcohols and anesthetics was made by Frangopol et al. from Bulgarian (click for full pdf) uses compression isotherms.  When adding a anesthetic like alcohol two things can happen either expansion or condensation of the film.  It is known that alcohols that form hydrogen bonds with water molecule are thought to disrupt normal membrane function by penetrating into membrane domains and hydrophobically interacting with the membranes.  Increasing the alcohol concentration thus will cause increase in membrane fluidity.  When the surface tension in the compression isotherm was measured it was confirmed that this could produce condensation in the membrane.  So ethanol can both penetrate the film and lower the substrate surface tension.   The alcohol also affects the phase transition temperature as well.  Based on the observations from the compression isotherms, calorimetry and some other experiments, the partitioning of alcohol into lipid membranes is governed by three major forces: (i) hydrophobic repulsion between alcohol and water (strongly favoring membrane partitioning); (ii) a much weaker attraction of the polar group of the alcohol to the head group of the lipids, and (iii) a weak repulsive effect due to the intercalation of the alcohol acyl group into the lipid bilayer.

It is a subject of much debate as to whether ethanol and anesthetics just affect the membrane and change the membrane proteins (embedded in the membrane) or whether ethanol and anesthetics disrupt the proteins directly.  The lipophilicity of ethanol and anesthetics as well as the very fast action of them makes me think more of the former being the more likely theory but it does not exclude the possibility for specific receptors.

PS1 One way to relieve some of these symptoms is to eat fatty foods (or just don't drink).  This is one reason why eating a big burger after a night of binge drinking might help you literally squeeze the ethanol out of the membranes so you can excrete it.

PS2 An interesting fact about redheads is that they need more anesthetic than others due to a defects in the melanocortin-1 receptor gene (MC1R) which also gives leads to the phenotype of redhair.  This gene MC1R gene may be involved with complex neuromodulatory regulation within the central nervous system and it is not quite clear as to whether a specific anesthetic attaches to it.