パリトキシンの恐ろしいメカニズム
Hello everyone, SCIENSPOT is a podcast that shines spotlight on the latest scientific
technology from Japan. Your host is REN from SCIENTALK. Today we are discussing research
from University of Tokyo that reveals the terrifying mechanism of Palytoxin, one of the
most potent toxins found in nature. This research finally explains how this deadly substance attacks
a fundamental component of your cells, the sodium-potassium pump. Palytoxin is associated
with severe, sometimes fatal, seafood poisoning from fish like parrotfish and pufferfish. It's
incredibly toxic, reportedly tens of thousands of times stronger than potassium cyanide.
What makes it so destructive is its target, the sodium-potassium pump. The pump is a vital protein
found in almost all animal cells. Its job is to maintain the necessary imbalance of ions,
specifically moving sodium ions out of the cell and potassium ions into the cell, against their
natural concentration gradients. It requires energy ATP to do this, acting like a microscopic
hand pump. For security, the pump has two gates, one internal, one external, that must never open
simultaneously. If they did, the concentration gradient, essential for nerve excitation and
muscle function, would collapse. To understand Palytoxin, you need to know the difference between
a pump and a channel. A channel is basically a simple pore or gate. It just allows ions to
flow naturally from high concentration to low concentration. The pump is much more sophisticated.
The research highlighted that pumps don't just open and close simple valves. They actually
destroy and regenerate the ion pathway itself in cycles. This extreme design ensures security,
preventing accidental leaks that would undermine the massive concentration difference the pump
is supposed to maintain. Palytoxin's action is simple, but devastating. It takes a highly
secure sodium-potassium pump and transforms it into a mere ion channel, a hole that lets
プラティオキシンの影響
nearly any positive ion flow right through the cell membrane. How does this transformation happen?
Researchers used cryo-electron microscopy, cryo-EM, to visualize the atom structure of the pump when
bound to palytoxin. The toxin, which binds from outside the cell, insert a plug deep into the
pump's ion pathway while the external gate is open. This plug stabilizes the outer pathway,
effectively preventing the outer gate from closing. The key discovery came when they added
the energy source ATP needed for the pump's cycle. Normally, when the pump prepared to
open the internal gate, the external pathway should disappear and close up. But because
palytoxin was plugging and stabilizing the outer pathway, the pump couldn't undergo its normal
structure change. Instead, an abnormal event occurred. The pump still managed to perform the
change required to open the inner gate. The result was the formation of a membrane-spanning bypass
channel, a new hole adjacent to the original pathway. Palytoxin itself helps construct the
walls of this bypass. Essentially, palytoxin acts by breaking the tight coordination
between the opening of the inner gate and the closing of the outer gate. This bypass allows
massive amounts of sodium ions to rush into the cell, causing the cellular overexcitation
and eventual destruction observed in poisoning. This research not only solved a long-standing
mystery about one of the world's most powerful toxins, but is also fundamentally clarifying the
core structural difference in the security principles between ion pumps and ion channels
in biology. Crucially, understanding this specific atomic mechanism opens a promising new avenue for
the development of an antidote to palytoxin poisoning, which currently has no treatment.
That's all today's science spot. So, I'm sorry for the delay in last week's episode. I was traveling
in Barcelona and Lisbon. My favorite parts of the trip were visiting Cosmo Caixa in Barcelona
and Lisbon Ocean Aquarium. Both spots are not yet well known in Japan, but their exhibits were
different from what you'd see in Japanese science museums and aquariums, which I found very interesting.
I'm planning to write a note about them with some photos, even though the text will be in Japanese.
Please feel free to check it out if you are interested. This podcast is broadcast in both
Japanese and English. I'd love for you to listen to the podcast and post your notes and post your
thoughts with the hashtag sciencepot. Thank you for listening and see you next time.
