In this video, I want to talk about
how the neuron resting potential is created,
and how it relates to concentration differences
in some of the important ions involved in neuron function.
Because understanding the concepts involved
in the neuron resting potential will
help us understand other neuron membrane
potential changes, like the graded potentials
and the action potentials.
So here I've drawn kind of a blown up neuron.
So we'll have the soma in red, the axon in green,
and one dendrite in blue.
And I've blown up the dendrite axon really large
just so I have some space to draw.
It's useful to consider the formation
of the neuron resting potential in imaginary steps.
But in reality, they all occur simultaneously.
So first, let's consider a neuron
with no resting potential.
So it's not more positive outside or more negative
inside the membrane.
And we'll consider that all these key ions have
the same concentration inside and outside the neuron.
So that there are no concentration gradients
for organic anions, potassium, sodium chloride, or calcium.
Now the neuron is going to be creating organic anions
and adding them to the cytoplasm.
And as organic anions are being created,
most of which are proteins with a net negative charge,
these extra negative charges that
are being added to the inside of the membrane,
are going to create a small membrane potential.
So that now it'll be more negative inside the membrane
of the neuron because of these extra negative charges.
But this will be something small,
like maybe it'll be somewhere around -5 millivolts.
I don't actually know what this would be,
but it's going to be some small membrane potential.
That's not going to be enough for the neuron to function.
But even with a small membrane potential
there will now be an electrical force
acting on the organic anions because they will be attracted
to the more positively charged outside of the membrane.
So that the electrical force will
be trying to drive organic anions out of the neuron.
But they won't be able to leave because it turns out
that the membrane is highly impermeable
to the organic anions.
And the same will be true for the diffusion force caused
by the higher concentration of organic anions
inside the neuron compared outside the neuron.
Even though these electrochemical driving forces
are trying to make the organic anions leave,
they can't get past the neuron membrane.
So they're trapped inside the neuron.
So no changes will happen to the concentrations
of the organic anions, and no further changes
will happen to the membrane potential
at this imaginary step.
The same is not going to be true for the other ions.
Because the neuron membrane has channels in its membrane
called leak channel, or leakage channels.
And these channels allow these ions
to pass across the membrane, although how easily these ions
ca cross the membrane to the leak
channels is very different for the different ions.
And these leak channels are open all the time.
They're not gated.
So they're not opening and closing in response
to some kind of stimulus.
For the next imaginary step, let's consider
what happens when we add the sodium potassium pump
to the neuron membrane.
So this is going to be our sodium potassium pump.
This will be an active ion transporter.
It will use the energy of one adenosine triphosphate
molecule.
I'll write as ATP for short.
To actively transport three sodium ions
outside the neuron in exchange for two potassium
ions being transported to the inside of the neuron.
Now by moving more positive charges outside the neuron then
it's moving inside the neuron, that's
going to make the membrane potential bigger.
It's going to make it more negative inside the neuron
membrane.
I'm not sure exactly what size of change
that would be but it's going to be something small.
Let's just say for example, it might be around -10 millivolts.
So now we have a bigger membrane potential.
But it's still probably too small for the neuron
to function.
Far more importantly than this change
to the membrane potential however,
is that we're going to have a big change
to the concentrations of potassium
and sodium inside the neuron.
By pumping potassium inside the neuron,
we will now get a much larger concentration of potassium
on the inside of the neuron than we
have on the outside of the neuron.
And by pumping sodium outside of the neuron,
we're now going to have a much smaller concentration of sodium
on the inside of the neuron compared
to the concentration of sodium on the outside of the neuron.
Now you may be wondering why the concentrations of potassium
and sodium changed inside the neuron.
But they didn't change on the outside of the neuron.
And the reason for that, is that the extracellular fluid, all
of this fluid outside of the neuron, is huge.
And the total number of ions outside the neuron,
and the extracellular fluid, is very large.
Compared to the volume of the cytoplasm inside the neuron,
and the total number of ions inside the neuron.
So that any of these movements of ions
across the membrane of a neuron, is really
going to only change the concentration of ions
inside the neuron.
And any change the concentrations
of ions in the extracellular fluid
is going to be negligible.
It's going to be so small it's not even worth considering.
There are now opposing forces on the potassium ions.
The electrical force will be trying
to drive these cations in to the more negative inside
of the cell.
But the diffusion force will be trying to drive potassium out
of the cell, from a higher concentration to a lower
concentration.
At typical neuron ion concentrations,
at this imaginary step, the diffusion force
would actually be much larger than the electrical force.
So while there are forces pointed
in opposite directions acting on potassium,
the net electrochemical driving force,
that is the larger diffusion force minus the smaller
electrical force, will cause a net movement
of potassium ions out of the neuron
through the leak channels.
As potassium ions are leaving the neuron
and carrying their positive charges out of the neuron,
that is going to make the inside of the neuron membrane
more negative.
The membrane potential is going to get bigger and bigger
with each potassium ion that leaves.
And it's going to continue to do so until the membrane potential
is big enough that the electrical force trying
to drive potassium ions into the neuron is the same size,
but in the opposite direction, as the diffusion force
trying to drive potassium ions out of the neuron.
When these forces are the same size and pointing
in opposite directions, there is no net movement
of potassium ions into or out of the neuron.
The occasional potassium ion will wander out
or wander into the neuron, but in basically even amounts.
For potassium, at typical neuron ion concentrations,
this might occur around -70 millivolts.
Which is more than enough of a membrane potential
for the neuron to function.
The membrane potential, where an ion
has balanced electrical and diffusion
forces so that there's no net movement
of that ion across the membrane anymore,
is called the equilibrium potential.
It's also called the reversal potential.
Now it actually doesn't take that many potassium ions
to exit the neuron, to reach the equilibrium
potential for potassium.
It's something like less than 1% of 1% of all the potassium
ions in the neuron have to leave for potassium
to reach its equilibrium potential.
So that the effect on the intracellular concentration
of potassium is really negligible.
This process does take a little time though.
Because most of the membrane is impermeable to potassium,
and they can only squeeze out through the leak channels.
Now for sodium ions, both the electrical force
and the diffusion force are strongly
trying to drive sodium into the neuron.
Because it's a cation, so it's attracted
to the negative inside of the neuron membrane,
and its concentration is much higher outside the neuron
than inside the neuron.
If we had a membrane that was only permeable to sodium,
these cations would flow into the neuron
until so many positive charges entered the neuron,
that it actually wouldn't be negative inside anymore.
It would actually become positive, at which point
the electrical force would switch.
And it would have to get quite positive inside the neuron
for the electrical force to get big enough
to balance the diffusion force, to reach the equilibrium
potential of sodium.
Which at typical neuron ion concentrations
may be around positive 50 millivolts.
Without input however, when the neuron membrane is at rest,
the permeability of the membrane to sodium
is actually quite a bit less than it is for potassium.
And in fact, the permeability of the resting neuron membrane
to sodium is something like 4% of that potassium.
So quite a bit less.
But because some sodium is able to squeeze through these leak
channels, bringing some positive charges into the neuron,
that is going to affect the membrane potential
a little bit.
So that instead of being at the potassium equilibrium
potential of around -70 millivolts,
at this imaginary step it might settle
in around -60 millivolts.
And that's actually a pretty typical neuron resting
potential.
When the membrane is permeable to multiple ions that
have electrochemical driving forces,
the resulting membrane potential is a weighted average
of the equilibrium potentials of those ions weighted
by their permeability.
At rest, the neuron membrane is much more permeable
to potassium ions than it is to sodium ions.
So that the resting potential is much closer
to equilibrium potential of potassium
than it is to that of sodium.
Because the concentrations and permeabilities of ions
are usually stable in most resting neurons,
the resting potential is usually stable as well.
Now neither potassium or sodium is
at its equilibrium potential, however.
So there will be a small amount of net movement
of both ions across the membrane.
A little bit of potassium will be dribbling out
of the membrane.
And a little bit of sodium will be dribbling into the membrane.
This will be matched by ongoing activity of the sodium
potassium pump, which not only creates these concentration
gradients in the first place, but also maintains them
over time.
The resting membrane usually has an intermediate permeability
to chloride ions, of around 45% of the permeability
to potassium ions.
In contrast to potassium and sodium,
whose concentration gradients play a big role
in creating the resting membrane potential, for chloride
the resting membrane potential plays a big role
in determining its concentration gradient.
The membrane potential drives chloride out of the neuron,
until its concentration gradient is big enough to balance it.
So that normally there's a very small concentration
of chloride ions inside the neuron compared to the outside.
And because of that, the equilibrium potential
for chloride is usually at or close
to the typical resting potential for a neuron
of around -60 millivolts.
Most neurons have other active means
of decreasing the intracellular concentration of chloride
though.
The main one being the chloride potassium symporter.
And this drives chloride out of the neuron
by harnessing the diffusion force acting on potassium ions.
So it lets potassium move out of the neuron like it wants to,
and it harnesses that energy to also push more chloride
ions out of the neuron, further decreasing the intracellular
concentration of chloride.
Because of this, the equilibrium potential
of chloride for most neurons is usually not
at the resting potential of around -60 millivolts.
But instead, it's around -70 millivolts,
which will cause some inward chloride flow,
leading to a minor change in the resting potential
to a more negative value.
Although usually the change is negligible.
Most neurons also have active means
to decrease the intracellular concentration of calcium,
so that there is a small concentration
of calcium ions inside the neuron compared
to the outside of the neuron.
The main one of these being the sodium calcium exchanger,
which I'll show right here, that drives calcium out
of the neuron by harnessing the energy
of the electrical and diffusion forces acting on sodium.
So that the calcium sodium exchanger allows sodium
to enter the neuron in exchange for pumping calcium out
of the neuron.
And this creates strong electrical and diffusion forces
trying to drive calcium into the neuron.
And these forces are so big that the equilibrium potential
of calcium wouldn't be reached until the inside
of the membrane was around positive 120 millivolts,
to flip the electrical force to balance the diffusion
force trying to drive calcium into the neuron.
But it turns out that the resting membrane permeability
to calcium is actually quite small.
So that it usually has little affect
on the resting membrane potential.
So while the concentration gradients
of chloride and calcium ions tend
to have little effect on the resting membrane potential
of most neurons, they do play major roles
in other aspects of neuron functions.
Which we'll talk about in later videos.