Anesthesia is the use of medicines to prevent pain during surgery and other procedures. These medicines are called anesthetics. They may be given by injection, inhalation, topical lotion, spray, eye drops, or skin patch. They cause you to have a loss of feeling or awareness. The mystery of anesthesia has been one of the biggest mystery in neuroscience. Surgery would be inconceivable without general anesthesia, so it may come as a surprise that despite its 175-year history of medical use, doctors and scientists have been unable to explain how anesthetics temporarily render patients unconscious.

Researcher Dr. Richard Lerner, the founder of Scripps Research’s Florida campus in Jupiter, describes anesthesia as the “granddaddy” of medical mysteries (mystery of anesthesia).

“When I was in medical school at Stanford, this was the one problem I wanted to solve. Anesthesia was of such practical importance I couldn’t believe we didn’t know how all of these anesthetics could cause people to lose consciousness.”

To shed some light on the mystery, Dr. Lerner and colleagues used a combination of nanoscale microscopy, cell studies, and experiments in fruit flies (Drosophila melanogaster). The fruit fly is a surprisingly powerful model organism in neuroscience.

They first exposed cells to chloroform, a potent anesthetic that doctors no longer use due to its dangerous side effects. They watched what happened using a powerful microscope “able to visualize biological complexes smaller than the diffraction limits of light.”

They 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.

“The TREK1 potassium channels release potassium, and that hyperpolarizes the nerve — it makes it more difficult to fire — and just shuts it down,” explains senior study author Dr. Scott Hansen, an associate professor at Scripps Research’s Florida campus.