Scientists unravel the mystery of anesthesia
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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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