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Study begins to unravel the 160-year old mystery of the mechanism of anesthesia.

Anesthesia, long considered a blessing to patients and surgeons, has been a mystery for much of its 160-plus-year history in the operating room.

No one could figure out how these drugs interact with the brain to block pain and induce a coma-like, memory-free state. The debate has divided the anesthesia research community into two camps; one that believes anesthetics primarily act on the cell membrane (the lipid bilayer) of nerve cells, perhaps altering it to the point that embedded proteins cannot function normally. The other says the membrane proteins themselves are altered directly by anesthetics.

Now there is new evidence supporting the latter position. A team of researchers from Weill Cornell Medical College has found that it is the proteins that are affected by commonly used anesthesia. Specifically, activity of ion channel proteins that are important for cell-to-cell communication is markedly reduced when anesthetics are applied, the researchers report in the Journal of General Physiology.

This is the first demonstration that anesthetics alter the function of relevant ion channels, in this case voltage-gated sodium channels, without altering properties of the cell membranes.  Importantly the studies tested clinically relevant concentrations of isoflurane, a widely used anesthetic. Previous studies that found the membrane was altered used much higher doses of isoflurane, concentrations that would never be used in patients.

The team studies the effects of isoflurane in neuronal cells using whole-cell electrophysiology, and on lipid bilayer properties using a gramicidin-based fluorescence assay.  Only at supra-anesthetic (toxic) concentrations did isoflurane alter cell membrane, lipid bilayer properties.

The team state that drugs are not perfect and they always have side effects.  And that the medical community can only improve drugs if researchers know how they work, which means that they need to know when drugs have non-specific or undesired membrane effects.

Now that the medical community has a basic understanding of how anesthetics affect cells in the central nervous system, they have knowledge to improve them.  In the future, researchers may be able to design anesthetics that do just what they want them to do, and not what they don’t.

Source:  Weill Cornell Medical College

 

Schematic of a lipid bilayer representing a simple cell membrane. A new study in The Journal of General Physiology shows that activity of ion channel proteins, which are important for cell-to-cell communication, is markedly reduced during anesthesia. Credit: Dr. Olaf Andersen.
Schematic of a lipid bilayer representing a simple cell membrane. A new study in The Journal of General Physiology shows that activity of ion channel proteins, which are important for cell-to-cell communication, is markedly reduced during anesthesia. Credit: Dr. Olaf Andersen.

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