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Professor Mark Saltzman: So, today we're going to
continue to talk about cardiac physiology.
In particular, the electrophysiology of the
heart which is quite interesting and important to heart function.
One of the--turns out that one of the most important diagnostic
measurements that can be made is through a device that was
designed by biomedical engineers called an electrocardiograph.
We'll talk about today sort of the origins of electrical
activity in the heart, the role that this electrical
activity plays in the function of the heart,
and then finally how--we'll talk a little bit about how one
can measure that electrical activity which comes from cells
in the heart, sort of deep inside your body,
but can be measured with electrodes on the surface of
your body. You'll get some more experience
with making those measurements in section on Thursday
afternoon. This is--I apologize,
a rather complicated diagram, but I wanted to show you a
picture that would give you a sense for sort of where the
electrical potential that all cells have comes from.
You know that cells are bathed in an extracellular fluid and
that that extracellular fluid contains molecules,
including ions or charged molecules.
In fact, the extracellular fluid is very rich in a
particular ion, sodium, and has lesser amounts
of other ions, potassium and calcium,
are the three most important in the electrical activity of
membranes; sodium, potassium, and calcium.
The extracellular space which is up on the top here is filled
with those ions, in particular,
has a high concentration of sodium.
The intracellular space, or inside the cell,
also is a water-rich environment and also has ions.
The ion composition inside the cell is different than the
composition outside the cell in that the sodium concentration is
relatively low. This chart here shows you for a
typical cell sodium concentration might be 15 mmol
while the extracellular sodium concentration is 145 mmol,
so almost ten-fold higher sodium ion concentration outside
the cell than inside the cell. Well, now you know from
what you know about the structure of lipid membranes
that charged molecules, even though they're small,
charged ions like sodium cannot penetrate through a lipid
bilayer, so there's no way for sodium to
get through this lipid bilayer. Even though there's a very
large difference in concentration,
these molecules of sodium on the outside can't diffuse inside
because they can't permeate through the lipid bilayer.
Now, potassium, notice, has a very high
concentration inside the cell, 120 mmol,
and outside the cell the concentration is low,
4.5 mmol, so again a big difference in potassium
concentration but going in the opposite direction.
If the membrane was permeable, sodium would diffuse in and
potassium would diffuse out but it can't through a plain lipid
bilayer. Well, you also know that
cell membranes are not just lipid bilayers.
They have proteins inserted in them and we talked about
proteins that serve as receptors, for example,
the insulin receptor that binds to insulin.
We talked about signal transduction through those
receptors a few weeks ago. We also talked briefly about
the fact that some of these proteins are transport proteins
and their role in the cell membrane is to allow molecules
that the cell needs to come in or to go out.
The glucose transporter is an example of that.
The only way that glucose can get inside cells to provide a
substrate for a metabolism is because there are specialized
proteins in the membrane that allow glucose to cross,
in the same way there are specialized proteins that allow
ions to cross. These proteins come in two
varieties. Some are active transport
proteins like this one which is called the sodium-potassium
pump. It's actually a little machine
that sits inside the cell membrane, it's a protein based
machine. Its job is to pump sodium out
of the cell and potassium into the cell;
sodium goes out potassium goes in.
It's moving those molecules against their concentration
gradients and so energy is required for that to happen.
It doesn't happen spontaneously,
you can't move molecules, molecules don't spontaneously
move from regions of low concentration to high
concentration. It requires energy and it gets
its energy from ATP. This is called the
sodium-potassium pump and it's ubiquitous in cells throughout
the body. It's how cells maintain this
low sodium concentration and high potassium concentration
inside. It's because they have these
little machines in their membranes that are continually
pumping sodium out and potassium in.
Does that make sense? It's the action of this pump
that causes these differences in ions to occur.
There are other proteins that serve as channels.
You can think of these as very specialized pores in the
membrane that allow ions to pass through, and they're selective.
This one is a potassium channel, and so if it is open it
allows to potassium to pass through.
It only allows passive transport.
It's not a machine like the other one, it's just a portal or
a hole that allows potassium to move down its concentration
gradient. If this potassium channel is
open, then potassium will naturally move.
It will move from high to low concentration,
that is, it'll move from inside the cell to out.
If sodium--if there's a channel for sodium and it happens to be
open, and that's what this is shown here,
a channel with the lid off means the channel is open,
then sodium can pass from its high concentration to low
concentration or from the extracellular space to the
intracellular space. The cell is in dynamic
equilibrium, that in its sort of steady state,
it's natural state, there is this active machine
that's pumping sodium out and potassium in.
Then, there are these pores that when they exist and when
they're open, are letting these molecules to
leak back the other way. The pump always has to be
operating because the leak is always happening.
Does that make sense? Because you have these
differences in ion concentrations across the cell
membrane these--and you have the flux of molecules continuously
across the membrane. What I've shown here are
channels that are--they have a lid on them so they're sometimes
open and sometimes closed, they can be both opened and
closed. Every cell in your body at a
given time is going to have lots of potassium channels that are
open and lots of sodium channels that are open.
They're just some that are open all the time.
Because of that there's a continual leakage of potassium
out of the cell and a continual leakage of sodium into the cell.
Well, if ions are moving across the cell membrane,
ions are charged molecules, and that movement is a current.
You usually think of currents as movements of electrons but
movements of ions, of positively charged ions,
is also current. So, there's a continual current
flow across the membrane. That continual current flow
causes a potential difference across the membrane.
Now, a membrane that's at rest, that is in its resting state,
is going to have a given number of channels of sodium and
potassium that are open. So, there'll be given current
of sodium that's flowing in and a given current of potassium
that's flowing out. That's being compensated by the
activity of this pump but this current flow creates a membrane
potential or voltage. Just like a battery,
because these currents are flowing, if I measure the
electrical potential on both sides of this membrane I would
get a voltage difference. It turns out that for most
cells that voltage difference is negative.
The inside of the cell is slightly negative compared to
the outside of the cell and it's in the range of -60 to -90 mV.
That's the backdrop, that's what you should think of
as sort of the resting state of a membrane,
it has these channels in it, it exists in this fluid
environment where there's high sodium outside,
high potassium inside, current flows,
membrane potential generated. To make it more complicated
there are certain of these ion channels that exist in open and
closed states. Those open and closed states
are regulated by the voltage across the membrane.
Here's one called the voltage dependent sodium channel.
The resting state, when the membrane voltage is,
let's say, -90 mV, the channel is closed,
and so this channel does not allow for sodium to enter.
If it opens, sodium now can enter through
new channels. If there are a lot of these
voltage-gated channels on the surface.
They sense a change in voltage, and they all open,
one can have a dramatic change in the currents that flow
through the membrane and hence a dramatic change in membrane
potential. Now, that's exactly what
happens when we have an action potential.
I show you this diagram that I showed you a few weeks ago when
we were talking about the nervous system and how it
communicates. I explained it in sort of a
superficial way then, but now you can understand it a
little better if you think about it in terms of these--of the
membrane and the membrane having channels that allow sodium and
potassium to flow. Under a resting condition they
have a population of channels that's always allowing sodium
and potassium to flow, that creates the potential.
Then, they have special channels that open when the
voltage is disturbed in some way.
Here, we're looking at a trace of membrane potential in
time. Imagine that you're very small
and you're sitting on the surface of this membrane but you
have special shoes on that measure the voltage or
something. You can experience the voltage,
the potential drop across the membrane by just standing on
this membrane. You're standing there in the
resting state, so you're watching sodium and
potassium go by because of their normal fluxes,
and the potential that you measure is, say -75 mV.
Now, something happens, there's some disturbance in the
membrane near you, not right where you're standing
but near you there's a disturbance.
That disturbance might be a number of events but what we've
thought about so far is that there's a neurotransmitter that
binds. Somewhere upstream of you
there's a neurotransmitter that binds to a receptor and it
creates a change in membrane potential.
A small change in membrane potential, but you feel it.
When you feel it at your sight there's also these voltage
sensitive sodium channels that exist in the membrane around you
and they go from the closed state to the open state.
In response to this small disturbance, some new channels
open, these happen to be sodium channels.
They open, a lot of them open because there's a lot of them on
your cell because your cell is designed to respond to voltages
so it has a lot of these kinds of channels.
Now, what happens when all these new sodium channels open?
There's a rush of sodium from outside the cell to inside the
cell. Sodium's positively charged,
you get a rush of current going by you, and that rush of current
depolarizes the membrane. Remember I said the membrane
had a negative potential, it's more negative on the
inside than outside, but all of a sudden you've
opened all these sodium channels and a rush of sodium goes in,
a rush of positively charged molecules go into the cell,
make the inside of the cell less negative because you're
adding a lot more positive charge to it.
That event is called depolarization.
If you were standing on the cell with your magic boots that
were electrically active somehow you would experience this
dramatic change in membrane potential.
The membrane becoming a lot less negatively charged,
even positively charged. That's due totally to this rush
of sodium through these new channels that have opened.
Well, there's a second set of channels called potassium,
voltage-gated potassium channels that also open but
they're slower than the sodium channels.
When they open they allow a lot more potassium to rush the other
way because, you remember, potassium is high inside and
low outside. First you get a rush of current
going in one direction, then you get a rush of current
going in the other. What causes in terms of
membrane potential is a rapid depolarization,
and then a rapid repolarization and these channels eventually
close again and the membrane returns to its resting state.
If you don't understand all the details of that,
that's fine, it's described in the book and
also described in other membrane physiology books that you could
go to. It's not important that you
understand all the details but that you have a sense for what's
happening, is that within this small
region of the cell membrane we focused on there was some kind
of a small disturbance, it opened all these
voltage-gated channels, caused rushes of current which
changed the membrane potential. That is, in this case what I've
described to you, is an action potential.
A small change here causes a large change at my local site,
and then I pass that on this way,
because I'm now standing at the site where there's a huge
disturbance in membrane potential and that's going to
cause some current to flow, a little bit to flow downstream.
That little bit that flows downstream is going to cause the
voltage-gated channels here to open, and an action potential to
be generated at this site. If you follow that line of
thinking, then an initial disturbance over here creates a
massive membrane potential here, which moves to here,
which moves to here, which moves to here,
and that's an action potential being transmitted down a neuron.
Make sense? That's what we talked about
when we were talking about the nervous system.
We were talking about information flowing from
dendrites, dendrites that have receptors for neurotransmitters,
those receptors for neurotransmitters causing a
small membrane disturbance which then gets converted into an
action potential. That action potential moves
down the axon, say in this direction to that
direction.
Why doesn't it move back? Why does it only move in one
direction? Well, it turns out that it's
very interesting physiology that when these membrane--when these
voltage-gated membrane channels get opened they become incapable
of being reactivated for some period of time.
The voltage-gated sodium channels open,
they close, and then they can't be opened again for some period
of time. Just a few milliseconds but
long enough for the action potential to pass out of their
region so that you don't get currents that flow like--or
action potentials that flow like this.
They only flow in one direction because these channels need to
recover. You understand now a little bit
more about why action potentials flow down axons and when they
reach these termini, the axon termini,
what do they do? This sudden change in membrane
potential activates a new process, and that new process is
release of neurotransmitter from the synapse.
That neurotransmitter then activates another cell,
generating an action potential, sending it down its axon,
and so on. In the nervous system
messages pass from neurotransmitter to action
potential, neurotransmitter, action potential,
neurotransmitter, action potential.
Because there might be many, many neurons impinging on one
particular neuron that I'm interested in and some are
sending positive messages, some are sending negative
messages, sending these little disturbances.
Whether this axon generates an action potential or not depends
on the sum total of the small disturbances that it's receiving
at any one time, Neurons can integrate
information.
That information is acquired from all the neurotransmitters
that are impinging on the dendrites that cause small
disturbances that may or may not add up to the large disturbance
which becomes an action potential.
You go on to study neuroscience or just physiology,
you'll learn more about this but I think you can probably
understand the basic concept. In the action potential and a
neuron we were thinking about a cell that had a receiving end,
that receives neurotransmitter inputs, that causes membrane
potentials to change, that somehow decides to
initiate an action potential. That action potential flows
very rapidly down this specialized process called an
axon, reaching the axon termini,
and then neurotransmitters are released to the next cell.
Heart cells are the same in that they contain these special
voltage-gated membrane channels, these voltage-gated ion
channels that allow for an action potential to form.
They're capable of doing an action potential because they
have these voltage-gated sodium and potassium channels.
Because of that, heart muscle cells fall into
the same category as nervous--of neurons in that they're in the
general category called excitable cells.
They're excitable cells, means they're capable of making
an action potential. To have an action potential
they need to have these specialized voltage-gated ion
channels in their membranes. Cardiac myocytes have that,
they also have actin and myosin.
They're muscle cells and they're capable of contracting,
meaning that this myocyte here can shorten itself.
It can make itself shorter by contracting just like a muscle,
a whole muscle contracts. That's different than
neurons so they have this capacity to transmit action
potentials; they have this capacity to
contract. Now, in muscle cells,
as we'll see in a few minutes, those things are linked.
When a muscle cell experiences an action potential it doesn't
do what a nerve cells does, which is pass that information
along to another cell via neurotransmitters,
instead it contracts. It also passes along the action
potential but it doesn't do that through a chemical synapse like
in neurons, it does it through an
electrical synapse in that these cells are very tightly welded
together. Remember we talked about in the
nervous system, the two cells don't physically
touch, there's a space in between
that's called the synapse and it's over this synapse that
neurotransmitters act. They're released from the
pre-synaptic cell and they create a change in the
post-synaptic cell. Cardiac myocytes are basically
welded together. In fact, there are special
junctions called gap junctions in between them that allow the
easy flow of current. If an action potential
flows through this myocyte, from this end to the other,
it doesn't have to--it basically flows straight into
the next cell because they're directly electrically coupled.
If an action potential arises and comes from this direction,
it flows very quickly down this membrane,
it causes this cell to contract, it flows right into
the next cell causing this cell to contract,
flows right into the next cell causing it to contract.
So, in cardiac muscle wherever the action potential starts it
contracts first, then the action potential flows
into the neighboring cells, they contract.
You can think about the cardiac myocardium, the sheet that I
showed you last time, the muscular walls of the
heart, as being sort of a sheet of these cells that are all
connected to each other. If I start an action potential
in one space, it's going to flow over the
surface. As it flows over the surface
cells will be contracting right behind it;
so electrical flow followed immediately by contraction
locally. Does that make sense?
You could imagine that this now--because they're directly
electrically coupled, signals can pass very quickly
over the surface of the heart. They can pass very quickly from
one to another, so I just need to start an
action potential in one place, it'll be propagated everywhere.
I might like to control that because I'd like to have the
heartbeat function in this controlled fashion we were
talking about last time. So how does the heart solve
this problem of control of how this wave of action potential
moves over the surface of the heart?
Well, it does that through a specialized group of pathways
that are collectively called the cardiac conduction system.
This is a terrible diagram. I'm going to show you the next
one, I'll show you a little bit better on the next one,
and so you'll see, it but imagine--just look at
the surface here. This is the heart,
the left ventricle, the left atrium,
the right ventricle, the right atrium,
and there's this pathway. The heart has something like a
nervous system in that this black region here is a pathway
that's called the cardiac conduction system.
It consists of several important points.
The first is called the sinoatrial node or SA node and
it's in the right atrium. The next point is the atrial
ventricular node which sits on a fibrous substance called the
septum which separates the atria from the ventricles.
The heart is kind of tilted to one side, it's not straight up
and down, so the atria are up here and the ventricles are down
here, there's a septum in between and
that's where this AV node sits. It turns out that this
septum is electrically insulating and so if a action
potential--a wave of action potential gets generated up in
the atrium, it stops when it hits the
septum, it doesn't move directly to the ventricles.
The muscles of the atrium and the muscles of the ventricle are
electrically isolated. The only point of connection
between them is this specialized fiber pathway called the AV
node. That AV node leads into a
series of branching fibers that are called the Purkinje system,
Purkinje fibers down here. These are fibers that very
rapidly conduct action potentials or electrical
signals. What I want you to see in this
slide is to notice that while all of these cells are
excitable, they have the property of
generating and sustaining an action potential,
they're excitable, an action potential can be
generated--the shape of the action potential varies in
different cells. That's all this diagram
shows you. You don't need to know the
details but notice that some things are different.
For example, in the SA node it's a very slow
rise of potential followed by a slow fall and then a much slower
rise again compared to ventricular muscle,
for example, that has a very rapid uptake,
a sustained depolarization phase and then a rapid
repolarization back to baseline. There are differences in the
ways that these things undergo action potentials.
What do you think that's based on?
What's different about these cells?
Well, if the action potential is the result of these
voltage-gated channels that must mean that ventricular muscle
cells have a different set of voltage-gated channels than SA
node cells. They might have totally
different molecules that are doing the transport or they
might just have different numbers of these molecules in
their membranes, but that's the difference in
physiology. What we're going to get to
the by the end here is I'm going to try to convince you that
this--these changes that are occurring in individual
myocytes, this rush of current that
underlies the action potential generation is what we measure
when we measure an EKG. That what you're measuring is
sort of the sum of all of these electrical potentials that are
occurring as your heartbeat changes in electrical--because
your heart cells are all experiencing changes in
electrical potential and because your body is basically a salt
solution which conducts electricity,
that you can measure those changes in electrical potential
happening in cells in the heart by having electrodes just on the
surface of your skin. The EKG arises from all of
these action potentials that are happening within all of the
thousands of cells within your heart.
This diagram is a little easier to understand.
It had more words than I liked so I blocked some of them out.
The other one are things that we've already talked about
before, the SA node is now familiar to you,
the sinoatrial node, the AV node,
this specialized bundle of His which carries potential--action
potentials very quickly from the AV node down to the Purkinje
system, and the Purkinje system which
branches throughout the ventricular wall.
How does--is a heartbeat regulated?
It turns out that some of these cells are capable of generating
their own action potentials. They don't need to be
stimulated by some outside disturbance;
they generate an action potential on their own.
The most famous of these is the SA node up here.
The SA node, if you look at it,
here's the action potential in the SA node, depolarization,
repolarization, now look what happens here.
The cell, when most membranes we've talked about are at
resting state, resting state such that their
membrane potential stays constant until its disturbed by
something from outside, this cell actually is slowly
changing its membrane potential on its own.
It does that with a very consistent frequency,
such that at some point this slow rise of action potential is
going--this slow rise of membrane potential is going to
go high enough that it causes its own disturbance and causes
its own action potential. This is called a
self-propagating action potential.
Cells like cells of the SA node that are capable of doing this
have special properties of their ion channels.
The end result is that the SA node is just making action
potentials on a very regular basis.
If you measured, if you put an electrode,
or if you shrunk yourself and you had your magic boots and you
could stand on the SA node, you would measure an action
potential about 60 times a minute.
Once a second, the SA node is just creating an
action potential. Now, when it creates that
action potential what happens? It disturbs the cells that are
around it. When the SA node creates an
action potential it causes a voltage disturbance in the cells
around it and they start making action potentials.
Starting from this source in the SA node, a wave of action
potentials starts to move over the atrium, over the atria.
First the right and then the left, and what happens as this
wave of action potentials spreads over the atria?
What happens--what else do muscle cells do?
They contract, and so a self-propagating
action potential in the SA node induces an action potential wave
that spreads over the atria, the atria contract.
They contract--if you watch them they contract from the
region of the SA node out to the right slightly before the left,
but it passes pretty fast over these relatively small surface
areas. Now, remember that there's
a septum in between the atrium and the ventricle so this action
potential wave would stop and not go down to the ventricle
except for the AV node. When the action potential comes
down these pathways, these specialized pathways from
the SA node, it reaches the AV node.
The AV node has another special property in that when it's
stimulated to make an action potential, it hesitates.
It hesitates for a fraction of a second and then it starts its
own action potential. So, it receives the
disturbance, it waits and then it makes its own action
potential. What happens?
Start to put the picture together now,
SA node action potential, wave of action potential of the
atria, contraction of the atria,
AV node gets the signal, waits, generates an action
potential and that action potential quickly propagates
down through the bundle of His in the Purkinje system.
What do they do? They carry this action
potential down into the ventricles.
They start action potentials in the ventricle,
which then passes a wave over the ventricular muscle,
and after that wave of action potentials comes contraction and
ventricular contraction. Now, why does the AV node
wait? It waits in order to control
the heartbeat in the way that we described last time,
so that you want the atria to contract and deliver their blood
to the ventricles before the ventricle starts to contract.
You want the ventricle to wait until it's filled up with blood
from the atrial contraction and then start to contract.
So, the AV node provides that separation in time of the atrial
contractions and the ventricle contractions.
Now, how would you like the ventricular--now remember when
the ventricle contracts it's a big contraction and wants to
force blood in what direction? Up out of the top,
that's where the pulmonary artery and the aorta are;
remember from the model they're up at the top of the heart.
So, you would like for this muscle to very effectively eject
blood out of the ventricular chambers and into these two
large vessels. You all have roommates,
true; I don't know if you all share
toothpaste with your roommates, but if you do then some
fraction of you, probably about half,
are irritated with your roommates because they grab the
toothpaste tube at the top. You might have brothers and
sisters who do this, they grab it near the top and
they squeeze it because they only care about getting their
little toothpaste out and so you get this--that's not an
effective way to get toothpaste out,
squeezing it from the top because some of the energy goes
down into the bottom and forces this toothpaste down here and
the thing gets all out of the shape.
What if you wanted to get all of the toothpaste out of the
tube on one squeeze, how would you do it?
You'd go from the bottom up, you'd starting squeezing from
the bottom and you'd squeeze it up.
If you were good at this, and you could practice this at
home, you get toothpaste and you could see how much of the--what
fraction you can get out with a single squeeze.
I think you'd find your best is to start from the bottom and
squeeze sort of systematically going up, and that's what the
heart does. That's why this Purkinje system
is here; too rapidly conduct signals
from the SA node down to the base of the ventricle and really
start the contraction down here. The contraction starts at the
bottom and squeezes up and the blood is propelled out.
One of the roles of the Purkinje system is to carry this
potential into the ventricles in a way that provides maximum
benefit from the contraction of the cells that result.
Now, a couple of other things that are interesting to
know here. One is that the SA node is not
the only collection of cells in the heart that are capable of
generating their own action potentials.
Actually the AV node is also capable of generating the action
potential and so are the cells in the Purkinje system.
They all can generate action potentials, but it turns out
that the SA node does it the fastest.
It does it about 60 beats per minute.
The AV node does it at maybe 40 beats per minute and the
Purkinje fibers do it at even a lower rate than that.
What does that mean? It means that the SA node is
functioning properly, the AV node doesn't matter what
it's doing in terms of automatic generation of potentials,
because that potential that was first generated by the SA node
arrives at the AV node before it generates its own potential.
Who determines the heart rate? The fastest beating automatic
cell and those are generally in the SA node.
What happens if you have a disease in your SA node and it
stops functioning? Then the AV node will take over
because it's no longer being stimulated by the SA nodes
action potential and the wave that results,
it will start beating but the heart will beat slower,
it will beat at 40 beats per minute let's say.
If you had some disease there and that didn't work anymore
than the Purkinje system--so the heart has sort of a failsafe
system built in such that if this automatic beat generator
fails there are inferior, not such good quality,
but still capable beat generators further down the
line. Often those--the AV node
itself, you're not going to be able to function in the same way
because you're not going to get the same cardiac output because
you're heart isn't beating fast enough.
There are ways to treat that now, and the most common
way of treating that is by putting a pacemaker into the
heart. The pacemaker is a device
designed by biomedical engineers, about the size of a
hockey puck, but now even smaller than that,
that sits in your chest and it basically does what the SA node
is supposed to do, generates a potential with a
very regular period. There's a wire that goes from
this artificial device into your heart, into the atrial muscle,
and sits there and stimulates the tissue around the SA node to
replace its function, so that's how a pacemaker works.
This technology has evolved to the point where there's sort of
wireless--you can send signals in,
you could change the rate, you can reprogram the pacemaker
without having to take it out and actually physically
reprogram it, so these are quite
sophisticated engineering devices now.
I said something about action potentials and ion
currents. I'm not going to say anything
more about that now. I will say that in neurons what
is important in a propagation of an action potential is sodium
and potassium, but in muscle cells calcium is
also a much more important player.
The reason that calcium is a much more important player is,
as you will learn if you study more physiology,
calcium is the most important ion in terms of initiating
contraction. So, movement of calcium around
muscle cells is very important. This just shows an action
potential in, for example,
a ventricular cell. It has this rapid upstroke,
this plateau in depolarization and this recovery.
So, this might be an action potential you'd record from a
ventricular muscle cell, and if at the same time you
were recording this action potential and you were also
measuring contraction. Think of this measurement as
how much contraction the cell has done, at this point in its
resting state and in this point it's in its most contracted
state, then the contraction follows
the action potential by about 100 milliseconds.
As the contraction happens--as the action potential happens the
contraction happens about 100-150 milliseconds after that,
the maximum response; but these things are coupled
but they're not simultaneous.
I think I've covered what's shown in this slide here.
This is just a simpler version of what we've talked about,
generation of the signal in the SA node, movement to the AV
node, hesitation. Then, movement of this signal
down the septum in between the left and the right ventricle,
through the Purkinje system, and the heartbeat being
generated in this regular anatomical pattern.
That happens because these specialized tissues are able to
conduct signals very rapidly, and you can see here in this
slide, this is how fast a signal the velocity of an action
potential being propagated through different tissues goes
very rapidly through pathways like through the atrium,
through the bundle of His, and very rapidly through the
Purkinje system. That's why the signal gets
transmitted so rapidly from the AV node down to the base of the
heart. These diagrams are in the Power
Points which are posted. I just encourage you to look at
them, together with reading the chapter and hopefully that will
help you to understand this process.
Which brings us back to thinking, at the end,
about what I've talked about several times during the
lecture; that is, that you can measure
something about the physiology of the heart by measuring all of
this electrical activity. One way to measure it would be
to put electrodes directly into the heart and physically put
them right near the site of action and measure exactly
what's happening. That could be--you could get a
very detailed picture of what's happening in the heart that way.
That can be done but that's an invasive process.
There are cardiologists that do that, they do this everyday on
people. They put a catheter into your
heart, a catheter that goes through one of the vessels,
an artery in your leg. It's pushed up into the heart
and then there are recording electrodes on the end and they
can measure electrical activity directly in the heart at
different locations. That's called cardiac
catheterization and cardiac electrophysiology,
and it's widely used to diagnose disease in the heart.
That's usually not the first thing you do because
that's an invasive procedure. What is important about EKG is
that it's not invasive. You can do it without entering
the body, by just measuring something that's happening on
the surface. You can do it very simply by
placing electrodes at different positions on the body.
You've all seen a diagram like this that shows a typical trace
of an EKG, it's measured in milivolt here,
it's a relatively small potential because there's some
distance--the potentials that were actually generated in the
heart are tens of milivolts, but you're measuring at a
distance away and so that signal's been attenuated,
you're only measuring fractions of a milivolt at the surface.
What you see is a little bump, followed by a delay,
followed by a very big wave, followed by a delay,
followed by one and sometimes two smaller waves.
This is the signal that you see--that you've seen on screens
by patients beds in countless movies and television shows.
What do these represent? Well, they're called by letters
of the alphabet. This one's called the P wave
that represents the activity caused during atrial
contraction, so all of those currents that
are generated during atrial contraction show up as a P wave.
The QRS complex, this very big signal here,
is contraction of the ventricle.
What does this represent here, the distance between the P wave
and the QRS wave? This represents the delay in
signal transmitting through the AV node.
If your AV node was not functioning you'd expect that to
shorten, that lag would shorten. You'd also expect that your
cardiac performance would not be so good, because you don't have
this delay then the ventricle is contracting before it's fully
filled by the atrial contractions.
You can diagnose that problem, somebody comes in,
they're short of breath, they're having trouble,
they don't know what it is, you measure their EKG,
you see that this is shortened and you know that there's a
problem with their cardiac conduction system,
in particular, with the AV node. That's how physicians use these
tools. The T wave is re-polarization
of the ventricles. This is the return of all of
this current back into the cell after this massive
depolarization. The U wave, which is only very
rarely seen, represents relaxation of the muscles,
the papillary muscles inside, which control some of the valve
function. We'll talk about this more in
section. If you've had a full
electrocardiogram you'll know that they put many electrodes on
your body. They put--a full
electrocardiograph would take 12 electrodes and some of them are
placed on your limbs and some of them are placed around your
chest, sort of wrapped around your
chest in a fashion. The reason for doing that is
that you can--if you put several electrodes then you could look
at the potential difference that's generated by looking at
any two of those electrodes. If I have one up here and one
up here and I look at the voltage difference here,
it might not be the same as the voltage difference measured
between here and here. Why is that?
Because your heart is oriented in space, it's a three
dimensional object. All of these cells are at
particular three-dimensional positions inside this three
dimensional object. As these currents happen they
happen in a very spatially oriented way.
So, the potential difference I measure at a distance,
here and here for example, is different.
It's sort of like looking at the heart from different
vantage points, looking at the electrical
activity of the heart from different vantage points.
One of the things that cardiologists have learned how
to do is how to look at potentials that are generated
from different spatial locations,
and correlate that with things that are happening over the
complex geography of the heart. Why do you have more than one
electrode? It's so you can look at the
heart from sort of different angles.
Questions? Good, see you on Thursday.