Scientists unravel the mystery of anesthesia
Scientists from Scripps Research have shown how anesthetics cause clusters of lipids in the cell membrane to break apart, triggering downstream processes that lead to a loss of consciousness.

In a recent study in the journal PNAS, scientists from Scripps Research in San Diego, CA, describe the mechanism behind general anesthesia in unprecedented detail.

A medical mystery:

• Researcher Dr. Richard Lerner describes anesthesia as the “granddaddy” of medical mysteries.

• Used a combination of nanoscale microscopy, cell studies, and experiments in fruit flies (Drosophila melanogaster).

• First exposed cells to chloroform, a potent anesthetic that doctors no longer use due to its dangerous side effects.

• Watched what happened using a powerful microscope, and found that chloroform shifted the organization of lipid clusters in the cell membrane, from tightly packed balls into highly disordered structures.

• As this happened, the lipid cluster also spilled its contents, including an enzyme called PLD2. The team tagged PLD2 with a fluorescent chemical so that they could watch it move away from the original lipid cluster.

• They found that the enzyme went on to activate molecules within other lipid clusters, including a potassium ion channel called TREK1.

• The activation of this ion channel essentially “freezes” neurons, so that they can no longer fire action potentials. This leads to a loss of consciousness.

“We think this is fundamental and foundational, but there is a lot more work that needs to be done, and it needs to be done by a lot of people,” says Dr. Hansen.

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