Anesthesia Turned On Its Head

Anesthesia…you wouldn’t have surgery without it. But do we have the whole picture on how it works? “Not yet,” says new research from New York City’s Weill Cornell Medicine. The study, published March 6, 2017 in the Proceedings of the National Academy of Sciences, found that anesthesia “induces unconsciousness by changing the function of proteins that reside on the surface of a thin membrane that forms a barrier around all cells.” The study is entitled, “Clinical concentrations of chemically diverse general anesthetics minimally affect lipid bilayer properties.”

“We have debunked a century-old hypothesis and finally have proof that these anesthetics must have a direct effect on integral membrane proteins—and not an indirect effect on proteins through the lipid bilayer—to put patients in a coma-like state, allowing them to undergo painful procedures with no memory or pain,” said co-senior author Hugh Hemmings Jr., M.D., Ph.D., in the March 6, 2017 news release. Dr. Hemmings is chair of the Department of Anesthesiology at Weill Cornell Medicine and anesthesiologist-in-chief at NewYork-Presbyterian and Weill Cornell Medicine.

“Over time, more and more studies suggested that anesthetics interact directly with proteins, in particular with those on the surface of the cell membrane such as ion channels, which are important for cell-to-cell communication,” said first author Karl Herold, Ph.D., a senior research associate in anesthesiology at Weill Cornell Medicine. “This protein theory contradicted the initial lipid based hypothesis, which stated that anesthetics affect neuronal function by changing properties of the cell membrane.”

Dr. Hemmings told OTW, “There has been controversy regarding the fundamental understanding of how general anesthetics work for 170 years. A lipid based hypothesis, in which anesthetics are believed to modify the cell membrane, has been challenged, but has not gone away despite considerable evidence that proteins are indeed potential targets for anesthetics. We attempted to settle this debate by determining whether or not anesthetics interact with the lipid bilayer in order to examine this early hypothesis more closely.”

“The most interesting finding is that in fact the lack of any membrane effect at all—to be more precise, at clinical concentrations we see no effect on the membrane, providing strong evidence against the lipid based hypothesis.”

“The take home messages for surgeons are that A) the development of modern clinical anesthesia opened up the entire field of surgery allowing more complex and longer surgical procedures and B) that these anesthetics do indeed work by interacting with specific protein targets rather than nonspecifically with the membrane.”