Every year, tens of millions of people around the world go under anesthesia for surgery. They breathe in a gas, drift off to sleep, and wake up hours later with no memory of the operation. It's one of the most routine parts of modern medicine. But here's the strange part: for 175 years, doctors didn't fully understand how it actually works.
That mystery has now been solved. Researchers at Weill Cornell Medicine in New York and Birkbeck, University of London have identified exactly where a common anesthetic drug called sevoflurane attaches to the body's cells to cause unconsciousness. Their findings, published June 19 in the journal Nature Communications, could eventually lead to safer anesthesia with fewer side effects.
The research focused on sodium channels, which are tiny proteins that act like gates on the surface of nerve cells. These channels control the flow of electrically charged particles in and out of cells, allowing nerves to send signals to each other. When someone breathes in sevoflurane, the drug slips into a small pocket in these sodium channels and stabilizes them in what's called an "inactive state" — basically, it makes the gates less likely to open. With fewer signals firing, the brain quiets down and the patient loses consciousness.
"Sodium channels are critical for communication between neurons in the brain, and anesthesia breaks down that communication," said Dr. Hugh Hemmings, senior associate dean for research and chair of the Department of Anesthesiology at Weill Cornell, who co-led the study. "So, there's good reason to believe that the unconsciousness produced by volatile anesthetics is related to their effects on sodium channels."
To crack the problem, the team turned to a surprising helper: a tiny marine bacterium called Magnetococcus marinus. Mammalian sodium channels are too large and complicated to study in detail, but this bacteria has a simpler version that works in a similar way. Using powerful X-ray machines, the researchers captured the first atomic-level images of sevoflurane bound to these channels.
"A bacterial channel that behaves like ours but is small enough to crystallize lets us finally see where sevoflurane sits and how it holds the channel inactive," said Dr. Karl Herold, co-first author and senior research associate at Weill Cornell.
The researchers also found that changing even a single building block of the binding pocket prevented the drug from working properly, confirming they had found the right spot.
The team is now working to apply these findings to human sodium channels. If naturally occurring variations in human anesthetic binding exist, studying them could help explain why some people react differently to anesthesia — and perhaps even shed light on the biology of consciousness itself. "The insights we gain from this study may enable us to design safer, more selective anesthetics, with fewer side effects," Herold said.