|
Why does inhaling anesthetics cause unconsciousness? New
insights into this century-and-a-half-old question may spring from research performed
at NIST. Scientists from NIST and the National Institutes of Health have found
hints that anesthesia may affect the organization of fat molecules, or lipids,
in a cell’s outer membrane—potentially altering the ability to send signals
along nerve cell membranes.
“A better fundamental understanding of inhaled anesthetics
could allow us to design better ones with fewer side effects,” says Hirsh
Nanda, a scientist at the NIST
Center for Neutron
Research (NCNR). “How these chemicals work in the body is a scientific mystery
that stretches back to the Civil War.”
At the turn of the 20th century, doctors suspected inhaled
anesthetics had some effect on cell membranes, an animal cell’s outer boundary.
Despite considerable investigation, however, no one was able to demonstrate
that anesthetics produced changes in the physical properties of membranes large
enough to cause anesthesia. But eventually, understanding of membrane function
grew more refined as scientists learned more about ion channels.
Ion channels—large proteins embedded in the relatively small
lipid molecules forming the membrane—are responsible for conducting electrical
impulses along nerve cells in the brain and throughout our body. By a few
decades ago, the prevailing theory held that inhaled anesthetics directly
interacted with these protein channels, affecting their behavior in some
fashion. But no one could find a single type of ion channel that reacted to
anesthetics in a way pivotal enough to settle the matter, and the question
remained open.
“That’s where we picked up the thread,” says Nanda. “We had
been looking at how different types of lipid molecules affect ion channels.”
While a cell membrane is a highly fluid film made of many
different kinds of lipid molecules, the region immediately surrounding an ion
channel often consists of a single type of lipids that form a sort of “raft”
that is more ordered and less fluid then the rest of the membrane. When the
team heard other researchers had found that disrupting these lipid rafts could
affect a channel’s function, they put to work their own previous experience
working with the channels.
“We decided to test whether inhaled anesthetics could have
an effect on rafts in model cell membranes,” Nanda says. “No one had thought to
ask the question before.”
Using the NCNR’s neutron and X-ray diffraction devices as
their microscope, the team explored how a model cell membrane responded to two
chemicals—inhaled anesthetic, and another that has many of the same chemical
properties as anesthetic but does not cause unconsciousness. Their finding
showed a distinct difference in the way the lipid rafts responded: Exposing the
membranes to an anesthetic caused the rafts to grow disorderly, freely mixing
its lipids with the surrounding membrane, but the second chemical had a
dramatically smaller effect.
While Nanda says the discovery does not answer the question
definitively, he and his co-authors are following up with other experiments
that could clarify the issue. “We feel the discovery has opened up an entirely
new line of inquiry into this very old puzzle,” he says.
