Now ion channels, I hope I've convinced you,
are pretty important things. And we can imagine
that blocking ion channels might have some
significant impacts for cells, and they do.
Some of these molecules, they are molecules
that can block channels and the consequence
of blocking can have some very significant
impact. The neurotoxic alkaloids for example,
an example of which is saxitoxin, that you
can see on the right, is produced by paralytic
shellfish toxin. What it does is, it blocks
sodium channels of neurons, and can cause
some significant damage, if not death as a
result of its actions. Another common neurotoxin
that blocks ion channels is tetrodotoxin.
Tetrodotoxin is the toxic substance produced
by puffer fish that is a delicacy in Japan.
You eat the wrong part of a puffer fish and
you're in trouble because it blocks the voltage-gated
sodium channels of nerve cells.
Now not all ion channel blockers are toxic,
and if used properly they may have medicinal
purposes. For example people who have heart
arrhythmias commonly are treated with mild
doses of blocks, of blockers of ion channels,
for either sodium or potassium, that are targeted
for specific cells. The result of this action
is to slow down spurious signals that are
otherwise causing the heart to be arrhythmic,
and the arrhythmia can go away. Another medicinal
use of ion channel blockers is those of the
antihypertension drugs that will block calcium channels.
Now there are other things that can be
channel openers. There are for
example substances that will open up, in this
case potassium channels, one of them you can
see on the right, and that's minoxidil. Minoxidil
is a vasodilator, and minoxidil is better
known as the hair grow treatment, Rogaine,
that stimulates the growth of hair cells.
This substance acts as a vasodilator because
it's actually opening potassium channels.
There are drugs that are used that are also
channel openers, and these include anticonvulsants
as you can see here. Ionophores are molecules
that are related to channel proteins that
we talked about here, but they're not proteins.
These are lipophilic substances that in many
cases are actually synthesized by organisms.
Now these substances include potassium ionophores
that will embed themselves in membranes and
selectively allow potassium to move. One of
the examples that you can see here is valinomycin
shown on the right. It has a relatively simple
structure and allows the movement of potassium
into a cell. Valinomycin can act as
an antibiotic because if it binds to
a target cell and disrupts the cell's potassium
gradient it can actually kill the cell.
Proton ionophores are interesting and important.
Now one of the really interesting ones here
is called 2,4 Dinitrophenol or 2,4 DNP.
Now 2,4 DNP first came into popularity about
100 years ago. Around the turn of the 20th
century, there was a miracle diet drug that
was released. The miracle diet drug was
2,4 DNP. And 2,4 DNP was advertised very
much like the miracle diet drugs that you
hear about today on the Internet. Those miracle
diet drugs of course involve taking a pill
and sleeping. While you sleep your fat burns
away. Well it turns out that with 2,4 DNP,
that actually did happen and the reason that
happened was because the 2,4 DNP allowed
protons to leak into the mitochondrion.
Now we saw that the ATP synthase was relying on
proton gradient, spinning that rotor to make
the ATP. What if you poke a hole in the dam
so the water, instead of going through
the turbine, comes in through the hole? Well
you will destroy the gradient, and if you
destroy the gradient, what's going to happen
to the synthesis of ATP? Well, of course it's
going to plummet. Well cells need ATP, so
when they need ATP, what do they start doing?
They start burning substances like glucose,
like fat, and so forth to generate the proton
gradient. But the more they try to generate
the proton gradient the more it simply leaks
through the hole. 2,4 DNP was a miracle diet
drug; it just killed a decent percentage of
the people who took it. So I always tell students
to think about this when I'm describing miracle
diet drugs and so forth, and one of the questions
I get from students after telling that story
is the following, what if you took just a
little bit? To which I say, well what if you
took just a little bit of arsenic, would you
do that? I don't think you would, so is not
a good idea. In any event, 2,4 DNP is
not something to mess with.
Other things that are ionophores that are
considerations are calcium ionophores. These
include ionomycin, and there are other ionophores
that will allow not just specific ions in,
but a variety of ions in, and these include
the compounds that you see on the screen here.
Well I've spent a lot of time here talking
about the importance of lipid bilayers, and
the lipid bilayers as they relate to both
the movement of ions, the generation of ATP,
the control of the environment in which the
cell exists. It's quite clear that the lipid
bilayer is essential for a living cell, not
only as a barrier against the rest of the
world, but for carrying out the functions
that a cell needs to perform.