[♪ INTRO]
It’s safe to say that general anesthesia
has made modern medicine possible.
So it might surprise you to hear that even
though doctors have been using
general anesthesia for nearly 200 years, they
haven’t known exactly how it works
in the brain to temporarily shut it down.
We know that anesthesia doesn’t just put
someone to sleep.
It’s closer to a temporary coma, where you
don’t respond to pain or other stimuli.
Your anesthesiologist can keep you in that
state,
and reverse it when it’s time to wake up.
But what’s actually happening in your brain
while that goes on has been a mystery...
until now.
There have been two main hypotheses
for how anesthesia works on a molecular level.
The first, called the lipid hypothesis,
has been around since the turn of the 20th
century.
That’s when scientists observed that the
potency of some anesthetics
directly correlates with their ability to
dissolve in oils.
Our cell membranes are made of oily molecules
called lipids.
And there are several anesthetic drugs that
are all oil-soluble.
So it made sense that an affinity for our
cell membranes
could be the key to how they worked.
But the lipid hypothesis started to lose support
after the membrane protein hypothesis gained
traction in the 1980s.
That’s when evidence was coming to light
that anesthetics
could bind to proteins in the membranes of
nerve cells,
as opposed to interacting with the membranes
themselves.
We’ve managed to identify several proteins
that bind with different anesthetics.
And protein binding is how most drugs work.
Still, that didn’t explain what those anesthetics
were doing after they were bound.
But a June 2020 study has revealed a major
clue
into the mechanism of general anesthesia —
and in this case, it’s actually consistent
with the lipid hypothesis.
The study was specifically interested in inhaled
anesthetics,
rather than injected ones.
It demonstrated that inhaled anesthetics disrupt
lipid rafts in nerve cells.
These are clusters of lipids that form part
of the cell membranes of neurons.
They seem to play a key role in the central
nervous system.
Studies suggest that lipid rafts are more
tightly packed than the
surrounding cellular membrane, and have a
slightly different chemical composition.
The researchers used a super high-tech microscope
to show lipid rafts
expanding and bursting apart like billiard
balls in response to anesthetics.
When the rafts bust apart, they spill their
contents, including an enzyme called PLD2.
Once on the loose, the researchers showed,
PLD2 heads over to a protein called TREK-1.
Once there, it binds to TREK-1 and switches
it on.
That causes it to open up and churn out positively-charged
potassium.
Nerve cells need a certain balance of charged
particles, including potassium,
to fire and do their jobs.
The potassium increases the charge of the
nerve enough for it to malfunction,
inhibiting the firing of neurons.
In other words, you’re out like a light.
Or so it went in fruit flies!
To image the rafts, the researchers used an
advanced microscope
that can pick out single molecules.
Lipid rafts are smaller than what you can
normally image using visible light —
a limitation called the diffraction barrier.
This technology finally provided enough resolution
to work around that barrier and actually visualize
the lipid rafts.
Which is how they were finally able to propose
an answer to such an old question.
We’re still not sure why this mechanism
exists —
obviously it didn’t evolve so surgeons could
use anesthesia.
Further research ought to shed light on why
our neurons do this...
billiard ball lipid raft thing.
It could also help scientists better understand
how neurons work,
and may reveal new treatments for nervous
system disorders.
So we finally have an idea for how some kinds
of general anesthesia work —
after over a hundred years of trying to figure
it out.
Which is pretty cool, and reassuring if you’re
headed in for surgery sometime soon.
Thanks for watching this episode of SciShow,
and thanks to our patrons,
who help us bring mind-blowing facts like
this one to an Internet near you.
If you’d like to get involved and help support
our family of channels,
check out patreon.com/scishow.
[♪ OUTRO]
