Download Transcripts/4_10 10-12 (pt.2) (McNichols

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Friday, April 10, 2009
Dr. Bevensee
SA = sinoatrial
I.
II.
III.
IV.
V.
Scribe: Marjorie Hannon
Cardio electro-physiology (and ECG)
AP = action potential
AV = atrioventricular
Page 1 of 7
Cardiac Electrophysiology [S17]
a. We will talk about what initiates the action potential and the different types of action potentials are that you will
see in the heart.
Cell Types in the Myocardium [S18]
a. Myocardial cells are the primary cell type found within the cardiac wall- these are the cells involved in
contraction and causing the ejection of blood into the system.
b. There are two predominate cell types within the myocardium: contractile and conductile.
i. Contractile- the predominate cell type. These contract in response to an action potential; they can also
propagate an action potential. We will talk about the mode in which they do so.
ii. Conductile- the cells of the sinoatrial node, the atrioventricular node, and the purkinje fiber system. These
are specialized cells that are not like the typical myocardial cells which are columnar shaped, striated
cardiac cells. These look more like fibroblasts; they are a more diverse cell type. These are not involved in
the generation of force. Instead, they have a specialized type of compliment of ion channels in the cell
membrane that allows for rhythmicity. We will talk about how this occurs. These cells are able to initiate
and propagate an action potential. What type of protein is involved in propagating action potentials
between cells? Gap Junctions: those are the type of proteins that are involved in both chemical and
electrical communication between cells. Each of these cell types are connected to each other electrically
via Gap Junctions- that is how the action potential is able to propagate from cell to cell.
Diversity of Cardiac Action Potentials [S19]
a. As well as having diverse morphological cell types, there is a diverse electrophysiology of different types of
cells in the heart.
b. This is showing the action potential profile of cells of the sinoatrial node (SA node). The membrane potential is
shown on the Y axis and time is on the X axis. The SA node cells have a neuronal-looking AP; more of a
sinusoidal type of AP when you compare the electrical activity in an AP within the atrial cells, purkinje cells, and
ventricular cells.
c. In the atrial cells, the duration of the AP is shorter than that present in the purkinje cells and in the ventricular
myocytes. The reason for this is the different types of ion channels that are present and the relative abundance
of channels in each of those cell types.
Equilibrium potentials of various ions for a mammalian cell [S20]
a. I wanted to remind you of the different equilibrium potentials that will be important in understanding the AP firing.
b. The membrane potential is very negative for a potassium ion; it is around -90 (based on relative concentrations
between the inside and the outside of the cell). Chloride ions also have a relatively negative membrane
potential. Sodium ions have a relatively positive equilibrium potential (so the reversal potential is very positive
for a sodium ion). That is going to be important in understanding why the AP profile looks the way it does.
Calcium ions have an even more positive reversal potential or equilibrium potential.
c. These are examples of physiological concentrations that you will find and equilibrium potentials relative to those
concentrations.
d. What is the equation that you use to determine equilibrium potentials? (She never said the answer).
Phases of the Fast Cardiac Action potential [S21]
a. There are different phases of the fast cardiac AP.
b. The depolarization phase, where the cell membrane potential goes from negative to positive, is phase 0. This is
the upstroke of the AP.
c. There is what is known as a repolarization notch where the cell will rapidly repolarize, and that is phase 1. How
that looks depends on the cell type within the myocardium. The reason for that are the ion channels that are
involved in that phase.
d. Phase 2 is the plateau phase.
e. Phase 3 is the repolarization phase where the cell membrane potential becomes more and more negative and
goes back to the resting potential.
f. Phase 4 is the resting potential of the cell. The resting potential is different in different cell types. The reason
for that is the abundance of the channel that is responsible for that resting potential.
g. Notice the length of duration of the action potential in comparison to that which you would find in a nerve action
potential. Recall in a nerve action potential, the whole AP is over within a few milliseconds; it is much longer in
the myocardium. One reason for this is because the heart needs time to allow for ions to move to allow for
contraction.
h. A muscle twitch is also shown in relation to the AP. There is a phase lag in the actual twitch developing in
relation to the electrical activity of the heart, of that myocardial cell (I think she meant that the twitch is of the
Cardio: 11:00 - 12:00
Scribe: Marjorie Hannon
Friday, April 10, 2009
Dr. Bevensee
Cardio electro-physiology (and ECG)
Page 2 of 7
myocardial cell?) This is because it takes time for the calcium to get into the cell and interact with the proteins
that are involved in contraction.
VI. The myocyte at rest [S22]
a. The myocyte rest is known as phase 4.
b. Recall from earlier lectures that the Na/K ATPase is involved in maintaining the electrical gradients between the
inside and the outside of the cell. There is a high concentration of potassium on the inside of the cell and low on
the inside. The opposite is true for sodium (there is a high concentration outside relative to the inside).
c. At rest, there are voltage gated sodium and calcium channels that are closed. There is a certain type of
potassium channel that remains open at rest, at negative potentials. Because these channels remain open and
they are not voltage gated channels, these allow for potassium movement across the membrane. Based on the
fact that the relative permeability is highest for potassium, that determines that the equilibrium potential for
potassium predominates the membrane potential. Therefore the membrane potential is very negative.
d. On the slide: The blob in the Vm should just be an arrow. Should read: Vm = -80  -90
e. Because the predominate conductance is potassium, the cell membrane potential remains very negative. But, it
is not quite at the equilibrium of potassium potential because there are slight conductances through other ion
channels.
VII. Ik1 inwardly rectifying K+ channel [S23]
a. The channel that is involved in maintaining the membrane potential at rest is known as the inwardly rectifying
potassium channel. It is known as that because of biophysical characteristics where it allows for conductance of
potassium easier in the inward direction than it does in the outward direction.
b. This is important in relation to electrical activity in phase 3, but at resting potential there’s a predominate
conductance that’s potassium. Because of that channel being open, the membrane potential goes toward E k so
you’ve got a negative membrane potential.
c. These are not voltage gated channels; they are voltage regulated because of these biophysical characteristics. It is because
of a physical block of the pore, it is not because of the biophysical change in conformation of the protein itself (which occurs
in voltage gated channels).
VIII. The upstroke- Phase 0 [S24]
a. The upstroke of the AP is phase zero and this is due to the activity of fast sodium channels; voltage gated
sodium channels (Recall the AP in a neuron- they are related proteins, but are not identical to a neuron’s).
b. At the resting membrane potential (RMP), these channels remain inactivated. Because they are voltage gated,
a wave of depolarization moves towards a cell, and that will raise the potential- it depolarizes the cell membrane
potential. When that cell membrane potential reaches threshold, the conformation of the sodium channels will
change and open up quickly becoming activated. They have fast activation.
c. Because of the concentration of sodium being higher on the outside and low on the inside, and the fact that the
intracellular potential is negative, there is a very high electro-chemical driving force for sodium to move into the
cell. Will that change the concentration of sodium within the cell or not? (To change the membrane potential). It
is not going to change it. Only a small number of the relative amount of ions has to move in order to change the
membrane potential so you are not going to get a change in concentration of sodium within the cell, it is the
membrane potential that is changing.
d. The fact that these open within a couple of milliseconds (fast activation) means that almost 90 degree upstroke
of the AP. The importance of that is rapid depolarization.
e. Fast inactivation occurs where there is another part of the protein that closes in. The activation gate remains
open, but that inactivation gate closes which blocks the pore and blocks sodium from moving through. That
occurs as an intrinsic gating mechanism that then closes down those sodium channels. These channels then
require a little bit of time in order to recover from that inactivation. That is involved in refractoriness.
IX. Phases of the Cardiac Action Potential [S25]
a. The refractory period is relative to the activity of the sodium channel.
b. The absolute refractory period- during that time, absolutely nothing can reinitiate another AP. You could have
any amount of stimulus and it will not open up the ion channel. That is an important mechanism because during
this time you want to maintain that plateau phase because you need time to increase the concentration of
calcium inside the cell in order to begin the process of contraction.
c. Again, during the absolute refractory period, nothing can stimulate another AP. That is very important because
it prevents tetanic contraction of those cells. If you have tetanic contraction of heart cells, the heart would not be
able to beat or pump blood, so this is a physiological advantage to that type of intrinsic gating of the sodium
channels.
d. During phase 3, some of the sodium channels will have recovered from inactivation and they have gone back
into their resting state. In this case, sufficient stimulus can begin an AP, but during that time the AP won’t look
normal – it has a different wave form. But eventually, as all of the ion channels recover from inactivation, a
stimulus that arrives at that cell will stimulate another AP to fire. During phase 3 if sufficient activity is present,
Cardio: 11:00 - 12:00
Scribe: Marjorie Hannon
Friday, April 10, 2009
Dr. Bevensee
Cardio electro-physiology (and ECG)
Page 3 of 7
you can actually stimulate arrhythmias. It is important that you can actually stimulate arrhythmogenic activity
during that phase (illustrated in the next slide).
X. Consequence of the state of activation of fast Na channels [S26]
a. During phase 3, the shape of the action potential changes until eventually all of the sodium channels have
recovered from activation and now a normal looking AP can fire.
XI. Phase 1- Early Repolarization [S27]
a. Phase one is known as the early repolarization phase or “Ito” (“to” stands for transient, outward current).
b. If you have an inward current you depolarize the cell. If you have an outward current you repolarize the cell. So
it makes sense, if you have transient outward current you are going transiently repolarize that cell membrane.
c. It is due to two components. Don’t worry about knowing each of these components, only to know that there are
different reasons for that repolarization notch.
d. You need to remember that the transient outward current, this movement of ions that causes an outward
current, will change the membrane potential of the cell and depending on how strong that effect is you can
actually repolarize much quicker in some cell types than you can in other cell types.
e. What would happen if you blocked the activity of either of these types of channels and stop that repolarization
notch? Would it increase or decrease the duration of the AP? Increase because it is not going to bring back the
membrane potential closer to the resting potential, so it is going to take longer for the other ion channels that are
involved in repolarization to bring that cell back to rest.
f. If you block those channels and you block that repolarization notch you can increase the duration of the AP.
XII. Phase 2- The plateau phase [S28]
a. There are two types of conductances that are active in the plateau (phase 2) phase (inward Ca conductance
and outward K conductance).
b. Calcium is very low inside the cell compared to the outside, so if you open up calcium channels you are going to
have a strong driving force for calcium to move into the cell.
c. We’ve already talked about the concentration gradient for potassium, but remember that during the plateau
phase the cell has become more positive. So now the cell is positive inside and there is a high potassium
concentration so the electro-chemical gradient is very strong for potassium to move out of the cell.
d. During the plateau phase, these two conductances are acting against one another and they balance each other
out. (that is the reason for the plateau phase)
XIII. Phase 2 [S29]
a. There are two types of calcium channels involved in the plateau phase and also involved in the slow action
potential.
b. The L-type calcium channel is the predominant type of calcium channel.
i. They are voltage gated channels, so as the cell depolarizes there is a conformational change that occurs in
that protein that then causes those channels to open up. (So they open up at depolarized potentials).
ii. Sodium influx causes the depolarization upstroke at phase 0. As it reaches around -10 mV, those channels
are then activated to open. That opens the conductance for calcium, the calcium then moves into the cell.
It is involved in the electro-physiological changes in the AP and it is involved in contractility.
iii. They have a slow inactivation. That is why they are called L-type- for Long lasting.
c. T-type calcium channels are much less abundant.
i. They are also voltage gated.
ii. Their activation occurs at a much more hyperpolarized potential.
iii. These are fast in activation properties, they are active transiently (which is why they are called T-type).
XIV.
Phase 2 [S30]
a. During phase 2, the potassium conductance involves a variety of different types of voltage gated potassium
channels. You do not need to know the different types, but know that there is more than one type. The relative
abundance of each of those channel types within different cells of the myocardium will lead to a difference in the
AP duration. This is because each of the potassium channels has unique biophysical properties- some open
slowly some quickly, some close quickly or slowly. It depends on the biophysical property how long the AP
duration will be affected.
b. Again you don’t need to know the different types, just know that there are different types of potassium channels
involved in the plateau phase.
XV.
Phase 3 [S31]
a. This occurs at the end of phase 2 and leads into phase 4. At the end of phase 2, because of a time dependent
closure of the calcium channels, those channels start to close down and you lose that calcium conductance. So
now the predominant conductance is potassium which will lead to a repolarization of the membrane potential.
b. Remember the Ik channels that we just talked about, that variety of channels that is involved in the plateau
phase- depending on their activity, it can alter the repolarization.
Cardio: 11:00 - 12:00
Scribe: Marjorie Hannon
Friday, April 10, 2009
Dr. Bevensee
Cardio electro-physiology (and ECG)
Page 4 of 7
c. The Ik1 channels are responsible for the resting membrane potential. Because of their intrinsic rectification
properties, as that cell membrane potential starts to move back towards more negative potentials, that block is
relieved and those channels are now able to conduct potassium. This then adds to the conductance that is
occurring through these voltage gated channels. It is sort of an additive effect.
XVI.
Action potential and underlying conductance changes in a ventricular myocyte [S32]
a. This is to illustrate the overall conductances that occur during the fast action potential. This is conductance vs.
potential.
b. At rest, the sodium conductance is virtually zero. As a wave of depolarization reaches that ventricular cell for
example, you will open up sodium channels. That will increase conductance of the sodium channels.
c. As the conduction to sodium increases, you will depolarize the cell membrane and the AP fires. There is an
initial decrease in potassium activity because of those inwardly rectifying potassium channels. As the cell
membrane becomes positive, those inwardly rectifying potassium channels stop being able to conduct.
Therefore, the conductance initially will decrease but as you depolarize the cell membrane, making it more
positive; you are going to activate voltage gated potassium channels. The conductance to those channels
increases and you also increase the conductance to calcium because the cell repolarizes, voltage gated
channels open up, and calcium conductance increases.
XVII. Pacemaker channels and automaticity [S33]
a. The pacemaker channels are involved in automaticity.
b. The cells of the sinoatrial node (SAN), the atrioventricular node (AVN), and the his-purkinje system fire
spontaneously. They have an intrinsic electrical activity that allows them to fire.
i. You can actually take the heart out of the body and place it in appropriate conditions where it is oxygenated
with salt solution; the heart will continue to beat rhythmically for a long period.
ii. The importance to that is, even when de-innervated, they can fire at rhythmicity. Those cells don’t need the
innervation from the autonomic nervous system in order to fire; but the autonomic nervous system is
involved in modulation. It is the balance of the sympathetic and parasympathetic nervous system that will
alter the rhythmicity of those cells.
iii. They don’t need innervation because they have intrinsic ability to fire off their own action potentials.
c. The rhythmicity is modulated by channels active at or near threshold. The pacemaker cells of the SA node do
not have such a negative potential at rest because of the relative abundance of the Ik1 type channel.
d. At rest there is a type of channel known as a HCN channel. When this channel was initially characterized by
electro physiologists studying myocytes, they described it as a funny current and called it “If”. It was called this
because it didn’t have the characteristics that were typical for other channels at the time it was being studied.
i. It is hyperpolarization activated, non-selective for sodium and potassium, and it is cyclic AMP dependent.
So it is called an HCN channel.
ii. You don’t need to remember the actual molecular nature of this channel other than to remember:
1. It is hyperpolarization activated, when the cell become negative that channel activates.
2. It is cyclic AMP dependent. If you change the activity of the sympathetic or parasympathetic nervous
system, you will change levels of cAMP. That will change the activity of the channels. It is through
the actual molecule of cAMP, not through another second messenger such as pKa.
3. It is non-selective for sodium and potassium.
iii. Remember that the funny current is the one that is active at the resting state of the cell.
XVIII. Slow Response Action Potentials [S34]
a. This is the fast type AP that we just talked about (top picture).
b. The slow type activity AP that you will find in the SA node is shown in the middle picture. The characteristics
are very different.
c. Notice first that the resting potential is much more positive than you will find in a ventricular cell for example or
even in an atrial cell.
d. Phase 4 is very stable in a ventricular or in an atrial cell, and here it is not stable. That is because of those If
currents, those funny channels that are present.
e. Phase 0 is much slower; it doesn’t have that perpendicular appearance.
f. The repolarization notch is absent. Why? There are no channels there to cause it- those channel types aren’t
present in those cells.
g. Phase 3 is slower in activity than that in a ventricular cell.
h. It is really important to remember that there is no fast voltage gated sodium channels present in these types of
cells. So you don’t have that rapid upstroke due to that fast activation of the sodium current.
i. It is also important to know that the depolarization phase is achieved by calcium currents. It is doing the same
thing, it is bringing inward positive ions into the cell, but the upstroke (that positive ion change) isn’t occurring
because of sodium currents it is occurring because of calcium.
Cardio: 11:00 - 12:00
Scribe: Marjorie Hannon
Friday, April 10, 2009
Dr. Bevensee
Cardio electro-physiology (and ECG)
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j. However, there is a sodium current that is involved in the upstroke in phase 4 and this is due to those If
currents. Remember that I just said that they are non-selective for sodium and potassium. At rest, there is a
high concentration of sodium on the outside relative to potassium.- the cell membrane potential is negative. The
electro-chemical driving force is stronger for sodium to move into the cell than potassium to move out of the cell.
So there is a sodium conductance that brings that cell to threshold. It has the same effects as a depolarization
from a neighboring cell but it is able to intrinsically bring that cell to threshold.
k. Again, it is predominantly sodium conductance that brings that potential more positive, it reaches the threshold,
and those calcium channels will activate. That carries the upstroke of the AP.
l. That is illustrated in the following slide.
XIX.
Chart [S35]
a. The funny currents are active at resting membrane potentials. As you hyperpolarize the cell, those
hyperpolarizated activated channels open carrying sodium into the cell and you get a depolarization. The
depolarization reaches a threshold potential.
b. Remember the T-type calcium channels have an activation potential of around -70 mV or so. As you reach
about -70 mV, those T-type channels are going to be activated and they carry the upstroke of the AP.
c. The L-type calcium channels are also involved. As the cell becomes more positive, they then become
activated and together they carry the upstroke of the AP.
d. As you depolarize the cell, you will activate k channels, similar to the ones you find in the myocardial cells.
e. So the conduction for potassium increases and the calcium channels close down.
f. Remember, the T-type channels are called transient because they are only active for a short period of time.
Those channels will close down quickly, so that plateau phase isn’t present. So you close down the calcium
channels, your potassium channels have become activated, and they will repolarize the cell.
XX.
The conduction system of the heart [S36]
a. The SA node is the primary pacemaker of the heart- that is important to remember. It is located in the right
atrium close to the vena cava.
b. Cells within SA node have that rhythmicic type of activity. They will initiate APs that then through gap junctions
electrically connect with other cell types of the myocardium in the atria. The wave of excitation passes down
through the right atrium, it goes over to the left atrium, there is a convergence of APs on the AV node and then
the wave of excitation passes down through the His bundle and purkinje system and reaches all areas of the
ventricular myocardium.
c. The SA node cells have an intrinsic ability to activate and conduct AP (transmit AP from cell to cell). The SA
node sets the normal rhythm of the heart, but dependent upon the activity of the sympathetic and
parasympathetic nervous systems you will have a change in the rate of APs firing. (Activity influenced by the
autonomic nervous system).
i. If the sympathetic nervous system predominates, it will increase
ii. If the parasympathetic predominates, it will decrease the rate of firing.
d. It connects with other elements of the conductile system
e. One of the things she wants us to memorize is the sequence of activation.
i. The SA node initiates the AP  the wave of excitation moves down through the atria  converges on the
AV nodethe wave of excitation then passes down through the bundle of His  through the bundle
branches  out to the Purkinje fibers  eventually reaches the ventricular myocytes.
ii. Memorize this normal sequence of activation in the conduction system.
XXI.
Organization of the AV node [S37]
a. This also an area of the heart that has rhythmicity – can initiate action potentials. But in contrast to the rate of
firing of the SA node, the AV node fires off a much slower rate. If you completely obliterate the SA node, the AV
node can act as the primary pacemaker of the heart.
b. It is important to know that whichever part of the heart is firing more frequently, that is the pacemaker of the
heart. You can have ectopic rhythm occurring at much faster rates than the SA node and that will predominate.
So, whichever goes fastest wins out basically.
c. Under normal conditions, the SA node is firing at much faster rate than the AV node and so the SA node will
drive the overall rate of firing throughout the heart.
d. Surrounding the AV node is connective tissue that is non conductive. So the wave of excitation passes down
through the conductile cells and converges on the AV node. There is only one pathway under normal
circumstances through which the wave of excitation can pass down to the bundle branches. That is important
because what you want to do is allow for convergence of that AP wave form and then allow for a uniform wave
going through to the ventricles. If that doesn’t occur then you get excitation of different parts of the ventricles
and they will not contract in unison.
i. There is a disorder known as Wolf-Parkinson-White syndrome where there are accessory pathways that
allow for conduction into the ventricles and they have no slowing down that occurs in the AV node.
Cardio: 11:00 - 12:00
Scribe: Marjorie Hannon
Friday, April 10, 2009
Dr. Bevensee
Cardio electro-physiology (and ECG)
Page 6 of 7
e. SQ: What is the difference between an AV bundle and an AV node? A: it is just the branching fibers that go
down through this connective tissue. They are all part of the same conductile system it is just different structure.
f. The AV node is where all the firing impulses converge. Then those impulses have to pass down into the
ventricles and the AV bundle is that structure present which allows for that transmission of the conduction of
impulses.
g. An important feature to know about the AV node is the conduction velocity within that cell type is very slow. It
slows the wave of excitation from the atria into the ventricles. An advantage to this is that the atria are allowed
to empty and contract before the ventricles start to contract themselves. The blood will actually go from the atria
to the ventricles.
h. The wave of excitation is slowed down in the AV node allowing for blood to go into the ventricles and then the
wave form passes down through the bundle fibers and into the purkinje system. Again, the advantage is that
the blood will be ejected from the atria into the ventricles and allow time for the excitation to occur within the
ventricles so that the blood is present in order to project.
i. The purkinje fibers are connected further down after the bundle branches. These conduct very rapidly. You
want the wave of excitation to go down into the ventricles, and then you want it to go really fast throughout the
entire ventricular myocardium so that each area of the ventricular myocardium is excited at approximately the
same time. The advantage for that is that the ventricles will contract in unison.
j. The purkinje fibers can also initiate APs and they have a very slow rate. If you have a block that occurs in the
AV node, then the purkinje system will take over and again these have very slow and irregular firing rate.
XXII. Gap Junctions [S38]
a. They are small pores that allow for electrical and chemical conduction between cells.
b. The relative number of gap junctions will then allow for an easier conduction pathway, so the wave of
depolarization from one cell to the next will be easier if there is a lower resistance pathway. So if there are more
gap junctions, it is like a sieve where the holes are large and the fluid will move through. If you have small
pores, it moves through more slowly. The more number or the larger the pores, the easier the flow because the
less the resistance- depolarization rate from one cell to the next will be quicker.
c. For example, in the purkinje fibers there are lots of gap junctions, so conduction velocity is faster because that
depolarization from cell to cell occurs quickly.
XXIII. Modulation of Electrical Activity of the Heart [S39]
a. The electrical activity of the heart is modulated by a variety of factors.
b. Electrolytes, pH, mechanical disturbances, autonomic nervous system, hormones, and drugs can influence the
electrical activity of the heart.
c. Mechanical disturbances, for example stretch of the myocardium can cause depolarization because there are
certain channels within the heart that open up when you stretch the membrane. If they allow positive ions to
move through, that will cause a depolarization of the cell and that can then initiate an AP.
d. There is activity of the autonomic nervous system. The sympathetic nervous system increase heart rate and
contractility. The parasympathetic nervous system will decrease the heart rate.
XXIV. Regulation of the electrical activity of the heart by the ANS [S40]
a. The heart can rhythmically fire all on its own, it doesn’t need the influence of the autonomic nervous system but
the autonomic nervous system will cause a balance of activity of the heart- it can change the rate of electrical
activity of the heart
b. Acetylcholines will modulate pacemaker activity.
c. The parasympathetic nervous system is inhibitory and the sympathetic nervous system is excitatory. In normal
healthy adults, the heart rate under normal conditions is relatively low because the heart rate is predominately
under the parasympathetic nervous system. If your heart rate is around 110 for example, then it is obvious that
it is more sympathetic activity occurring.
d. If you block the impulses of the autonomic nervous system from reaching the heart, then you will reach an
intrinsic heart rate and that is due to activity of the SA node.
e. Under normal conditions, only the SA node is the predominate pacemaker but under pathological conditions,
even ventricular myocytes that don’t have those funny type channels can cause a depolarization. For example,
if there is ischemia, then you can have a potential difference between two cells. That potential difference can
cause a current movement from one cell to the next and that can initiate an AP.
XXV. The parasympathetic Nervous System [S41]
a. Acetylcholine (Ach) will decrease the activity of If. Remember that If, the funny current, is cAMP dependent. If
you decrease cAMP due to the activity of the parasympathetic nervous system then you will reduce the
steepness of phase 4.
b. Draws on board: a slow wave action potential in a SA node cell.
i. This phase 4 is due to the activity of the funny currents. As those channels open up, the steepness of this
can change. Under parasympathetic activity when cAMP levels are low, those channels that are
Cardio: 11:00 - 12:00
Scribe: Marjorie Hannon
Friday, April 10, 2009
Dr. Bevensee
Cardio electro-physiology (and ECG)
Page 7 of 7
dependent on cAMP are going to be less active. This will make the wave form go towards the dotted line- it
will take longer to reach threshold and this slows down the rate of firing (slows down the heart rate).
c. It also reduces the activity of calcium channels because calcium channels are regulated by cAMP via pKa.
d. If you increase cAMP, you increase pKa, that will increase the open probability of those channels and you will
increase the conductance through those channels.
e. Remember, in the slow wave, the upstroke is due to the calcium channels. If you increase or decrease the
activity of the calcium channels, you will influence the change in voltage over time. If you decrease their activity,
you will slow down the upstroke of the AP.
f. The IkACh channels are related to the Ik1 type channels that are present in the ventricular and atrial myocytes.
If you open up a potassium channel, you make the membrane potential more negative and it will take longer to
reach threshold.
g. Collectively, these events will slow down the heart rate:
i. Potassium channel that brings the membrane lower (will take longer to reach threshold)
ii. Calcium channels that are less active (the upstroke of the AP will be slower)
iii. Decreasing activity of the funny current (slow down the upstroke of the resting state of the cell)
h. The AV node slows conduction velocity by inhibiting calcium channels. Because there is a decrease in the
upstroke of the AP the depolarization will be less. Conduction velocity falls. The heart rate is slowed in the SA
node and the conduction through the AV node is also affected.
XXVI. The Sympathetic Nervous System [S42]
a. The opposite is true for the sympathetic nervous system.
b. You will increase the funny current- as you increase cAMP levels you increase the activity of these channels. It
will increase the rate of change of upstroke of the resting potential. You will fire off an AP more quickly.
c. If you increase calcium channel activity, the upstroke of the AP will occur at a faster rate.
XXVII. Mechanisms involved in changes of frequency of pacemaker firing [S43]
a. This illustrates what she drew out on the board. Take some time to look through this to understand the rate of
firing.
b. SQ: Why does cAMP increase it? A: it binds to the If and by binding; it causes an increase in its open probability
allowing for more potassium to move through. It is a direct binding rather than a phosphorylation event that you
would see in other channels such as the calcium channel. cAMP actually regulates its activity directly. The
higher level of cAMP, the higher activity of that channel. The lower the level, the less cAMP available to bind, so
the activity of the channel will change. cAMP in the calcium channel acts through protein kinase A that
phosphorylates the channel and that changes the activity. So, it depends upon the ion channel. In this case it is
direct binding; in the case of the calcium channel it is a phosphorylation event- just a different way to alter the
activity.
[end 48 min]