Hi, everyone welcome to this tutorial on the ionic basis of the action potential.
What we're going to talk about today relates once again to one of our core
concepts in the field of neuroscience, and that is that neuroscience communicate
using both electrical and chemical signals.
So today we're going to talk about one of the most important mechanisms within the
nervous system for communicating with electrical signals We have some learning
objectives for you today. I want you to be able to revisit the
Goldman and even the Nernst equations and use those equations to gain an even deeper
intuition about the membrane potential of neurons.
To actually predict that value given knowledge of the concentration gradients
of ions and their relative permeabilities across the neuronal plasma membrane.
I want you to be able to describe the ionic basis of the action potential in
terms of both the voltage and time depenedent changes in ionic permeablities
that occur, that occur across the neuronal plasma membrane.
I want you to be able to describe the driving force for current flow across the
plasma membrane. Driving force will be an important concept
that will help you understand the movement of ions through the ion channels that give
rise to the action potential. But also through other kinds of ion
channels that are gated not by voltage but by neurotransmitters so that discussions
coming up in a few tutorials. Now as you work through these
considerations I want you to relate with careful precision the time course of the
changes in sodium and potassium conductance.
Back to changes in the membrane potential during the course of the action potential.
And lastly we'll talk a little bit about what's called the refractory period for
the generation of the action potential. So I would want you to be able to
characterize and discuss that concept. Okay, well let's begin by reviewing some
of our foundational concepts that we introduced last time.
And that is that changes in membrane permeability underlie the neuronal action
potential. And in order to understand these changes
in membrane permeability, let's consider some of the principles that are laid out
in figure 2.7. Now recall that during the resting state,
there is a little bit of potassium conductance.
That is, a little bit of potassium leaks out of the neuron.
So the permeability of the neuron at rest for potassium is some small value that's
greater than zero. However, the permeability of that resting
membrane for sodium is just about nil. So, even though the potassium permeability
is small, it's still very much greater than the permeability for sodium.
So what this means is that in the resting state the membrane potential is very close
to the theoretical limit predicted by the[INAUDIBLE] potential for potasium.
Now if we imagine some mechanism that allows for dramatic increase in the
permeability of the membrane for sodium. We may find ourselves in a situation where
the permeability for sodium is so much greater than the permeability for
potassium that the membrane potential becomes predictable.
By the Nernst equilbrium potential. Or the Nernst equilibrium equation for
sodium. Such that the membrane potential
approaches this theoretical value that we can calculate.
The Nernst Equilibrium potential for sodium.
And this is essentially what happens during the generation of an action
potential. The permeability of the membrane goes from
being just a little bit leaky for potassium, to now being explosively
permeable for sodium. And that will explain the rising phase of
the action potential. The falling phase, what we find next, is a
bit more complicated. But essentially what we can say is that
the permeability for sodium returns back towards zero and meanwhile the membrane
restores its resting state where the permability for potassium is considerably
greater. Then the negligible, or the nil
permeability for sodium. Okay, now in order to review all of this
and yet a different mode of learning I would encourage you to consider our, our
formal expression for these changes provided by The Goldman Equation.
And again, I would remind you that The Goldman Equation allows us to calculate an
equillibrium potential when there may be multiple ions that can permeate through
the membrane. So this equation includes a permeability
term. For each ion that we might be interested
in, And it also includes the concentration gradient, which allows us to consider the
Goldman equation as an extension of the Nernst equation for permeate ions.
Now maybe this more formal approach is less useful to you.
That's okay. If that might be you, then I would
encourage you to review these basic concepts of electrochemical equilibrium.
Using the animation provided on the website that supports our text book.
So you can click on the link in your tutorial notes, or navigate to that
website following the link on our website. And select animation 2.2 on
electrochemical equilibrium. And that will put you in great shape to
understand the concepts that we need to consider to explain the ionic basis of the
action potential. Well, finally before we get there I'll
just remind you that what we talked about last time is that changes in membrane
permeability Could have predictable consequences for the change in membrane
potential. Now, what we're going to try to explain,
beginning in this tutorial, is how is it that changes in membrane potential can
impact membrane permeability? Now, much of the work that I'm going to
tell you about in this tutorial And the next one that follows is based on the
seminal work of two really, just amazing figures in the history of nerve science.
Alan Hodg, Hodgkins, and Andrew Huxley. They were both scientists working in
England during the time of the second world war, or actually just before it, was
when their interests were being peaked by the possibility of recording bioelectrical
signals From nervous tissue. And then, World War II intervened.
And, well, depending upon who you are, what your family background is, and the
circumstances of your family's journey to where you are today you might consider
yourself fotunate that, that great war ended as it did.
At least those of us in the field of neuroscience are very gratetful for the
success of the allied forces because that allowed Hodgkin and Huxley to return in
the mid to late 40s to their work understanding the ionic basis of the
action potential. This work was recognized by the Nobel
Committee in 1963, when together with Sir John Eccles, an Australian scientist, they
were awarded the Nobel Prize in Physiology and Medicine.
I would encourage you to read about their biographies, including that of Doctor
Eccles, at nobelprize.org, where you can also find their Nobel lectures.
Well, what Hodgkin and Huxley did as one means of beginning to explore the ionic
basis of the action potential was to construct some circuitry that allowed them
to do the kinds of experiments that they wanted to conduct.
They recognized that in nature. We often have wonderful animal models that
allow us to address the questions that we want to ask.
In their case, they chose to examine the giant axon that's present in the body of
squid. Which were readily accessible to these
investigators in their location in the world.
Now, in order to study the ionic bases of the action potentials, they wanted to
measure ionic currents, but there's a bit of a problem.
Because with generation of an action potential, there is a change in membrane
permeability that will alter the flux of, Of ionic currents in a way that would make
it very difficult to con-, to control and to measure those ionic currents.
They devised a circuit called the voltage clamp.
And, this voltage clamps circuit is illustrated here from your text book.
I don't intend to burden you with the details of this, but I do want you to know
that for those of you that are interested, you can read more about this circuit
there. Essentially, what this circuit does, is it
provides us with an opportunity for measuring.
Ionic current, without changing the membrane potential.
Hence this term, voltage clamp. We can essentially clamp the voltage of an
excitable neuronal membrane to any potential that we wish, and thereby
measure. The movement of ions across that membrane
as we do these kinds of experiments. So I mention all this to say that we do
want to look at a couple of experimental results derived from studies that Hodgkin
and Huxley did, as a means of understand the ionic basis of the action potential.
So let's begin. Now what we have here in figure three
point one from your book is a representation of the kind of data that
were available to Hodgkin and Huxley. With the voltage camp, clamp method, they
were able to set the membrane potential. Of the squid giant axon to any value that
they wished. And here in this experiment, what's being
done is a hyperpolarization of the axonal membrane by 65 millivolts.
So they're going from a resting value of about 65 millivolts down to about 130 and
then they're holding the membrane or clamping it at that potential through some
period of time. And they are measuring then the current
that can be recorded during this experiment.
So what's seen is a sharp transient, which is called capacitive current.
This reflects the way charge is redistributed around the membrane.
But otherwise nothing significant is happening.
So with hyperpolarization there are no significant effects on net current that's
flowing into or out of the axon. Now when they passed a de-polarizing
current step into this neuron or in other terms when they clamped this neuron at a
marked depolarizing level. That is around zero millivolts so they
oppose this depolarization step. They saw something quite different and
quite remarkable. Following a sharp transient current, what
they saw was a transient inward current that, That was followed by a delayed
outward current. Now just a word about convention here.
In these experiments, inward currents are those carried by positively charged ions
into the cell, and our convention is to denote that as negative whereas outward
currents are currents carried by positively charged ions that are.
Leaving the cell, and this is denoted in positive terms.
Now there are other more complicated scenarios that we'll eventually discuss
involving negatively charged ions, but for now we can keep it simple.
So inward current means positively charged ions are entering the cell, and outward
current means positively charged ions are Exciting the cell.
Okay, well what we want to be able to do is to understand the underlying changes in
ionic fluxes that are explaining these two kinds of currents that were recorded.
A transient inward current and a delayed Outward current.
And in order to get there Hodgkin and Huxley were able to use both some theory
and also some impirical investigation of this system.
So the theory comes in the form of the Nernst Equation, so Hodgkin and Huxley
knew about the equilibrium potentials for permeate ions even though they weren't
sure what those ions were at the time that they began their experiment, they knew
that in principle. One could determine or manipulate a ionic
species that you think might be permeating the external plasma membrane.
And use the Nernst equation to calculate the impact of that permeable ion, given
it's known concentration gradiance. Well I'll just remind you then that the
nerdist equation is a tool that can be used in studies of this sort, and I'll use
that equation to remind you of this concept of equilibrium potential.
So remember at equilibrium potential There's no net movement of current.
So in an experiment like this we would record a current of zero at
electrochemical equilibrium. So again, this is the point where the
concentration gradient for a permeate ion is exactly counterbalanced by the
electrical gradient that builds up with the movement of that charged ion.
Now knowing these two facts it's possible to do experiments then, where we can
manipulate the membrane potential of an axon or of a neuron and allow for a
prediction on the movement of that ion. And as should be intuitively obvious to
you, I think, if you choose to clamp the membrane potential at the equilibrium
potential for a permeation, then that ion is no longer going to, going to contribute
to the measured current. Because by definition, at equilibrium
potential there's no net movement of the ion.
Okay, so these are the kinds of considerations that are brought to bear in
the following experiment. So now, what is being described, and
figure 3.2 from the textbook Is the results of producing an experiment now
where there are incremental changes in the voltage clamp setting in the depolarizing
direction. So we're starting off at rest, somewhere
around 65 millivolts. And we are now applying a depolarizing
current step from rest to different values of depolarization.
First approaching zero millivolts and then even going beyond zero millivolts.
That is making the inside of the cell more positive than the outside of the cell.
And what we see is that as we begin to depolarize this membrane from rest, there
is indeed a transient inward current followed by a delayed outward current.
But notice the magnitude of these currents.
With small depolarizations, the currents that are measured are relatively small.
With larger depolarizations, like around zero millivolts The transient inward
current increases in size as does the delayed outward current.
But now look at what happens to the transient inward current as we depolarize
to plus 26 millivolts. This transient inward current is getting
smaller. But, look at the effect of the delayed
outward current, it continues to grow in magntitude.
Now, we approach plus 52 millivolts in the experimental data and what we find is,
obviously, quite a large growth of the delayed outward current.
But notice, the, the transient inward current seems to have gone away
completely. We'll come back to that point in just a
moment, but now let's move on. If we depolarize the cell even further,
again we continue to see growth of the delayed outward current in a relatively
monotonic fashion as we change membrane potential in the depolarizing direction.
But now look at the point in time where we earlier recognized a transient inward
current. What we see is a small inflection in the
rise of this outward current. In fact, what appears to be happening is
that the transient inward current is no longer inward.
But outward. And this might explain this small shoulder
effect that we see in the development of this outward current.
Okay. Well, these considerations allow us to
make. A couple of points.
First of all, we see that this transient, inward current appears to be nulled out
with membrane potential around 50 millivolts.
And then when we go beyond 50 millivolts or, in this result perhaps precisely 52
millivolts. This inward current reverses.
It becomes an outward current. The second observation we make here is
that the delayed outward current steadily increases with increasing depolarization.
Now, we can measure these currents at particular points in time and plot their
magnitude as a function of membrane potential.
And when we do that we have data that look something like this, which capture again
what we've just described. And that is, that with depolarization, the
transient inward current grows. But we eventually hit a point of reversal
and that delayed inward current becomes an outward current with the crossing of 0
millivolts being somewhere around 50 millivolts in membrane potential
magnitude. Now the delayed outward current behaves
differently. It continues to grow monotonically with
increasing membrane potential. Now, these observations together again
provide evidence That this transient inward current reverses near 50 millivolts
while the delayed outward current increases steadily.
Now, knowing something about the ions that are present in seawater and having some
sense of what the ionic contributions might be to the cytoplasm within axons.
Knowing something about the Nernst equation, and then having the ability to
manipulate some of these empirical parameters in the experiment, allowed
Hodgkin and Huxley to identify What are in fact the ions that are carrying these 2
kinds of currents. What they concluded is that the early
current is carried by sodium. Now the nuanced equilibrium for sodium
happens to be very close to plus 52 millivolts in their experimental.
Preparation. That is highly circumstantial evidence
supporting this conclusion that the early current is carried by sodium.
One way to test that hypothesis would be to change the solution that is bathing the
neuron. And if you substitute the solution with
one That removes all sodium, the prediction would be that the inward
current ought to reverse to become an outward current because even though the
normal physiological concentrations of sodium are much greater outside than they
were in compare to the inside. If you artificially remove all sodium from
outside the cell, there will be a concentration gradient favoring the
efflux, or the outward flux, of sodium. And that appears to be what is recorded in
this experiment. And then returning back to normal
physiological conditions, similar to what we find in sea water, the inward current
is once again restored. This conclusion is further supported by
experiments using a toxin found in nature, a toxin called tetrodo-toxin.
Found in the pufferfish and when that toxin is applied to this axon, what we
find is that the transient inward current is blocked.
All we're left with is a delayed outward current with the application of
tetrodotoxin. So that result provides additional
empirical evidence. Supporting the conclusion that the early
current is carried by sodium. Now, additional experiments were done
using a tetraethyl-ammonium ion, which is now known to block potassium channels.
And when that ion channel blocker is applied to this preparation, what we find
is that the delayed outward current Is removed.
And all that we find is the transient inward current.
So this is very good evidence supporting the conclusion that the late current is
indeed carried by potassium ions. Okay.
Well I think we are ready to move on in our consideration of these data and I want
to introduce an additional concept that I think helps us come a little bit closer to
the underline biological mechanism that explains the ionic basis of the action
potential and this concept that I want us to think about Is conductance.
Now, we're familiar with Ohm's law from our study of physics.
Right? And so Ohm's law is v equals i r, or
voltage equals current times resistance. Well this concept of conductance, while it
has more of a formal expression. For our purposes we can represent
conductance by the lowercase letter g, and simply state that it's comparable to the
inverse of resistance. So it's possible, then, to rewrite Ohm's
Law in terms of current. And what we can state, then, is that
measured current is proportional to the conductance for that permeant ion times
the voltage. Now this voltage term is interesting.
This voltage term provides the driving force for the current that we can record
that is passing through a neuronal membrane.
But in order for that current to actually flow not only must there be a driving
force but there also has to be some means by which that ion can pass through the
membrane. Which is to say, there needs to be
conductance. So I want you to appreciate, using this
version of ohm's law, that current flow really requires two kinds of functions.
There needs to be conductance greater than zero, and there needs to be some voltage
that creates a driving force term. And so rather than saying that the voltage
needs to be greater than then 0 of what we need to express is that the voltage must
be greater or different from the nuanced equilibrium potential for the permiant
ion. Okay.
So this allows us now to return to our experimental situation where we changed
membrane potential and recorded current but now we get to introduce.
This version of Ohm's Law that helps us understand the movement of ions in terms
of the conductance of the membrane for the permeant ion.
So again, what we have here is a current which can be measured experimentally.
We know something about the membrane potential of the neuron and, given the
concentration gradient of, of the[UNKNOWN] ion, we know it's Ernst equilibrium
potential. So the driving force term then becomes,
the difference Between the membrane potential at any point in time and the
nernst equilibrium potential for the permeant ion.
So what would happen then, if the membrane potential is exactly the nernst
equilibrium potential for the permeable ion?
Under that situation, the driving force is equal to zero.
And no net current is going to flow. This is one way to establish
electrochemical equilibrium for a permeant ion.
That is, it's possible with the patch-client method to set the membrane
potential exactly to the nerve's equilibrium potential for the ion in
question. Well, this formulation should make it
obvious that there is another way in which to have no net current flow for an ion.
And that is when conductance is equal to zero.
That is when there's no means by which an ion can cross a membrane.
There may be a driving force, but if there's no conductance then the measured
flow of that current is going to be zero. Okay, well these are some theoretical ways
of considering the experimental results obtained by Hodgkin and Huxley and what's
shown now in the lower part of figure three point three are the same Data.
Except now, the measured ionic current is expressed in terms of the conductance that
is associated with the transient current and the delayed outward current.
Now having confidence that, that In that transient current is carried by sodium,
and the delayed current is carried by potassium.
So what we can now do is express these current fluxes in terms of conductances
for sodium and potassium. So let's look at these one at a time.
When we look at the conductance change for sodium with depolarization, what we see is
a very sharp and steep rise in sodium conductance that happens with increasing
depolarization. So it should be obvious then that the
sodium conductance is voltage dependent. But look what's going on here, even with a
sustained depolarization, this conductance, that quickly rises well above
zero, falls back towards zero. Even though we continue to clamp the axon
membrane to some value, as indicated here in the figure.
So this tells us that this conductance is not only voltage-dependent but it's also
time-dependent. Actually, the same conclusions can be made
with respect to the potassium conductants, but in a different way.
What we see is with increasing depolarization there is a growth to this
potassium conductance. So like the sodium conductants, there's
evidence for voltage dependency. But notice The growth is gradual, and the
onset of this conductance is slow relatively compared to the onset of the
sodium conductance. So there's an element of time dependency
that we see for the potassium conductance. Now, that conductance does not fall back
down sharply the way we saw for the sodium conductance.
Rather, the time dependency is in the relatively gradual onset of this rise in
potassium conductance that we see. So nevertheless, both conductances are
time dependent. But the time dependency seems to suggest
that there may be different molecular Mechanisms that mediate those time
dependencies. Okay.
Let's return now to the sodium conductance and make an additional point about this
rapid fall in sodium conductance. That we see after the rapid rise.
So, we actually have a term for this, we call this, inactivation.
Now, as we'll see in the next tutorial, inactivation is not exactly the same
mechanism as simply closing. An ion channel.
So we're going to want to understand that point in the next tutorial, but for now,
I'll just highlight the fact that the sodium conductance inactivates.
And what we mean by that is this rapid fall in conductance that follows the rapid
rise. Now notice, the potassium conductance does
not inactivate. So there's no inactivation of the
potassium conductance. Now there are certain types of potassium
conductances that can be found in certain neurons that do in fact inactivate much
like the sodium conductance, but not this conductance.
Not in this axional membrane from which these experiments are derived.
Okay I think we're ready to put all this together now and have.
A computational model that explains the action potential.
So, what we have here is a precise alignment of the voltage and time
dependent changes in sodium and potassium conductance.
Relative to the action potential. And I want you to spend a little bit of
time thinking about this figure, figure 3.8.
And considering the alignment of these conductance changes with what we see in
membrane potential. And the conclusion of such a thought
process is that the action potential is indeed explained by the voltage and time
dependent changes in the permeability of the neuronal membrane to potassium and to
sodium. Now let's look first at the sodium
conductance and how it's aligned to the action potential.
There is a sharp rise in sodium conductance that occurs in time, with the
rise in Membrane potential during what we call the rising phase of the action
potential. In fact, the rising phase is explained by
this rapid increase in sodium conductance. Now, we haven't explained yet how that
itself got started. But we'll come to that in the next
tutorial. For now, I'll simply state that some
external stimulus was applied to this experimental situation.
Or, if we can imagine, a real neuron or a real axon in a real brain, some stimulus
in the form of incoming electrical signaling activity, potentially can
depolarize that cell and produce this explosive increase in sodium conductance.
That explains the rising phase of the action potential.
But, again, let's notice that the increase in sodium conductance is short lived.
Soon thereafter, there's this falling phase, which we call inactivation of the
sodium conductants. And in terms of the membrane potential
that can be recorded, this is called the falling phase of the action potential.
So we have the rising phase on the up slope, and now the falling phase on the
down slope. Now this sodium channel on activation.
I know I'm getting ahead of myself just a little bit with respect to the tutorial
notes, but it does allow us to explain an important phenomenon called the refractory
period. So there's a period of time during which
it's not possible to generate another action potential And that's called the
absolute refractory period. That's happening during this time of
sodium channel inactivation. Because in order to generate another
action potential, these sodium conductances need to be reset back to
zero. So this inactivation Has to be removed in
order for another action potential to fire.
So the period of time during which the sodium channels are progressing through
their inactivation state, is in fact the period of time that we call the absolute
refractory period. Alright, so let's now turn to the
potassium conductance. The potassium conductance is delayed
relative to the onset of the sodium conductance.
But it's also sustained for a longer period of time.
And this sustained conductance for Potassium.
Allows potassium to flow out of the cell, and that means positive charge is leaving
the inside of the cell. This delayed outward current, or delayed
potassium efflux, contributes now to the falling phase of the action potential.
And notice that at the conclusion of the falling phase of the action potential, the
membrane potential actually undershoots the resting membrane level by just a small
degree. So this is called the undershoot.
And it is explained by the ongoing efflux of potassium ions.
Now, when we first considered the ionic basis of the action potential in
principle, it was sufficient to say that the resting membrane potential is.
Approximated by the Nernst equilibrium potential for potassium.
Now, we can state that that's not exactly the case.
The Nernst equilibrium potential for potassium is actually much closer to the
nadir of this undershoot. The actual resting membrane potential,
I'll call it v rest, in this case is about minus 65 millivolts, not quite where
the[UNKNOWN] equilibrium potential for potassium would be because there are other
complications, other Ionic fluxes that we haven't taken the time to consider and,
and that's okay. We can simply state that the resting
membrane is not an ideal membrane permeable only to potassium.
If it were, then Vrest would be precisely Ek.
But these is a small offset and that allows us to explain This undershoot.
Now, we've been emphasizing the time dependencies of these conductances.
I don't want to overlook their voltage dependencies.
So as the action potential is its falling phase and undershoot phase This membrane
is now becoming hyperpolarized relative to rest.
And as it does so, the potassium conductance trails back down towards it's
starting point. So as the membrane is hyperpolarizing.
Returning towards rest and then undershooting rest, the potassium
conductance is shutting down. Okay.
Well these considerations allow us to consider just a couple of other aspects.
Of action potential behavior that are worth noting.
We've talked some about this concept of threshold.
Now, I think, we can approach this in a bit more of a formal way.
We know that there is some thing like a threshold.
We saw that a couple of tutorials ago, where when exceeded there is a Runaway
positive feedback cycle, where membrane depolarization leads to increased sodium
permeability. So sodium rushes into the cell and that
leads to even further depolarization. This is the rising phase of the action
potential. Well, that's accomplished when we
stimulaate the axon or when the axon And the neuron receives stimulation from some
other source, such that the threshold for generating this positive feedback cycle is
exceeded. So we might call that a super threshold
depolarization. Now we can also move the cell in the
depolarizing direction away from rest and not hit threshold for firing an action
potential. That would be what we might call the
subthreshold depolarization. So what's the difference?
What's the difference between a depolarization that achieves threshold and
one that doesn't? Well the difference is whether that
depolarization crosses threshold, and threshold therefore can be defined as the
membrane potential when the sodium current is Exaclty equal to the potassium current.
That is, it's a tipping point, where just as much potassium is able to leave the
cell as sodium entering the cell. Now, because the sodium conductance opens
so much more quickly than the potassium conductance, Depolarizations of a
sufficient magnitude are certain to trigger an action potential.
Because we know that it's possible for so much more sodium to enter the cell than
potassium leaving the cell that we're driving this cycle past threshold and
generating the rising phase of the action potential.
Another way to conceptualize this is to consider the regenerative nature of the
action potential. We've been talking about this vast
positive cycle where sodium is entering the cell, leading to further
de-polarization and the opening of even more sodium-permeability channels that
increase sodium current and further de-polarize the membrane.
Until the point at which that conductance begins to inactivate.
So this is a picture of exceeding threshold and running this fast positive
cycle. But we also have a slower negative cycle,
and this is set into motion as the membrane begins to depolarize and the
permeability channels for potassium begin to open up more slowly, but as they do
Potassium channels are opening, potassium is leaving the cell, and this leads to
more of a negative feedback promoting the repolarization and eventually the
undershoot of the membrane potential. Now, it's interesting is it not, that the
negative cycle is slow. And the positive cycle is fast.
This, this temporal dependency ensures that the action potential can be an
explosive event. That is, the rising phase can happen
unimpeded by this more slow negative phase.
However, the negative phase eventually does dominate Yes the sodium conduct-ants
is beginning to en-activate but the potassium conduct-ants will drive the
membrane back to resting levels and even below rest to undershoot.
So the slow negative cycle. Seems to be nature's way of ensuring a
rapid signaling event that is an action potential of a short duration.
Now there are action potentials in nature that can be longer because other ion
channels are involved, but our Canonical action potential that we find in axons and
neurons is of this sort: a sharp rising phase followed by a sharp falling phase,
with an undershoot. Now, this slow negative cycle also allows
us to explain the rest of the refractory period.
I mentioned that the absolute refractory period is when sodium conductances are in
their inactive state, and it's not possible to trigger a second action
potential until that inactivation state is removed.
However, there is a relative refractory period that will be present As long as we
continue to have this slow negative cycle turning away, which is to say the membrane
potential is an undershoot. Now during that time it is possible to
trigger a second action potential because this sodium permeability channels are
ready to fire again. However with undershoot they're Is,
therefor, a need for a slightly stronger stimulus that can overcome that undershoot
and bring the membrane potential to threshold in order to fire an action
potential. That's why this refractory period is said
to be. Relative.
Well, together then, this fast positive cycle, this slow negative cycle, allows us
to understand the shape and the duration of the action potential, and it also
raises some interesting philosophical points, I think.
It suggest that there is a limit to the speed of processing in the nervous system.
And that limit is defined by the width of the action potential.
Of course that limit is actually an aggregate of the billions of action
potentials that are happening all the time in neural circuits and neural systems.
But in principle, there is a limit to what can be defined as the moment.
In fact, the aggregate consequence of this action potential width, is that our brain
is perpetually living in the past. We are processing right now information
that just happened. A few tens, or perhaps even hundreds of
milliseconds ago. No, I'm not talking about memory.
I'm talking about the brain working on the incoming flow of information.
And because of the width of the action potential, and as we'll see in a few
sessions, the delay that comes with synaptic transmission, it takes some time
to elaborate our thoughts and our perceptions and our emotions.
So from that standpoint, we would seem to be at something of a disadvantage, living
in a world in real time knowing that our brain is living perhaps a few hundreds of
milliseconds in the past. But.
Brains are wonderful organs. One of the best things they can do is
predict the future. If fact, our brains are constantly
updating our model about the future, so that we can anticipate the actions that
happen in real time in the world. So even though the width of the action
potential imposes a bit of a delay. In our neural processing we make up for
that delay by being able to predict behavior in the future.
Well, enough of that philosophy for the moment.
I think we're ready to wrap this up. And I'll leave you with a study question.
Which you can find at the bottom of your tutorial and you can find it online in our
next slide. So, consider this regenerative nature of
the action potential This fast positive cycle and the slower negative cycle.
But I want you to think about, why is the action potential a spike?
That's sometimes the term that neurophysiologists use to describe the
action potential. Which of these factors listed below do you
think is the best explanation for the short duration of a typical neuronal
action potential? Okay.
I'll see you with the next tutorial.
