Cardiovascular physiology Lecture-3

What is the Pacemaker?

Pacemaker is the structure of heart from which the impulses for heartbeat are produced. It is formed
by the pacemaker cells called P cells.
Where is the pacemaker?
Sinoatrial (SA) node is a small strip of modified cardiac muscle, situated in the superior part of
lateral wall of right atrium, just below the opening of superior vena cava. The fibers of this node do
not have contractile elements. These fibers are continuous with fibers of atrial muscle, so that the
impulses from the SA node spread rapidly through atria.

Action potentials and impulse conduction

Action potentials in the heart:

- Action potential in cardiac muscle is about 10-15 times longer than that of skeletal muscle.
- Cardiac action potentials are of 2 types:
1. Non-pacemaker potentials (in the atria and ventricles)
2. Pacemaker potentials (in the SA and AV-nodes)

 Phases of non-pacemaker action potential:

Action potential in a single cardiac muscle fiber occurs in five phases:
1. Phase-0 (Depolarization).
2. Phase-1 (Initial repolarization).
3. Phase-2 (plateau).
4. Phase-3 (Final repolarization).
5. Phase-4 (Restoration of resting membrane potential).

1. Phase-0 (depolarization):
- An action from a pacemaker cell causes the membrane potential of adjacent cardiomyocyte to
raise form the resting value of −90 mV by opening Na+ channels.
- Na+ influx will raise the membrane potential towards the threshold potential of −70mV.
- When the threshold potential is reached, more Na+ channels will open rapidly so that
depolarization becomes very rapid and the amplitude of depolarization will spikes up or
overshoots passing the zero point to a positive value of about + 20 mV in very short period of
time.

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2. Phase-1 (Initial repolarization):

- Initial repolarization is due to the following:
 The Na+ channels close.
 The K+ channels open causing efflux of potassium and returning the membrane potential
to approximately 0 mV.

3. Phase-2 (Plateau):
- Plateau is due to opening of Ca2+ channels.
- There will influx of calcium ions.
- Calcium ions entering the muscle fiber from the extra-cellular fluid play an important role in
the contractile process by binding to troponin and starting cardiac contraction.
- K+ ions keep leaking out.
- These two ionic movements (K+ out and Ca2+ in) counteract each other, and the membrane
potential is maintained at a plateau just below 0 mV throughout phase 2.

4. Phase-3 (Final repolarization):

- Ca2+ channels close.
- Efflux of K+ continues.
- Number of potassium ions moving out exceeds the number of calcium ions moving in. this
will restores the inside electronegativity, resulting in final repolarization.
- Potassium efflux continues until the end of repolarization. In this this phase, the original
membrane potential of – 90 mV is restored but with the fact that ions now had changed their
positions (K+ inside and both Na+ and Ca2+ are out).

5- Phase-4 (Restoration of Resting Membrane Potential):

 At the end of final repolarization, all sodium and calcium ions, which had entered the cell
will move out, potassium ions will move in, by activation of Na +-Ca2+ pump, Ca2+-ATPase
pump and Na+-K+ ATPase pump.

Refractory period
Defined as the time from phase 0 until the next possible depolarization of a cardiomyocyte, i.e. once
enough fast Na+ channels have recovered, in which the cells are incapable of further depolarization
and contraction. Cardiac muscle has a long refractory period compared to skeletal muscle; this has
advantages:

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1. Summation of contractions does not occur.

2. Fatigue does not occur.
3. Tetani does not occur.
4. Allowing sufficient time for the ventricles to empty and refill prior to the next
contraction.

Types of RF:
- Absolute refractory period (ARP): the cell is completely unexcitable to a new stimulus
because all the sodium channels in this period either are already open or are closed but
exhausted and therefor are inactivated. It lasts approximately 200 msec. and starts from phase
0 to the start of phase 3.
- Relative refractory period (RRP): During this period, the voltage-gated sodium channels are
closed, but yet they can open by a stronger than normal stimulus and if this occurs, then
another action potential will generate and another contraction will occur. It starts from the
terminal part of phase 3 up to beginning phase 4, therefor it is much shorter (about 50 msec).

Pace-maker potential (Action potential in SA-node):

The differences of SA-nodal cells with that of the rest of the heart are:
- The resting membrane potential in the SA-node is NOT a truly resting, it is an unstable
resting membrane potential and it is called (pacemaker potential or prepotential).
- RMP in SA node has a negativity of –55 to – 60 mV: It is different from the RMP in
other cardiac muscle fibers with a value of –85 to –95 mV (this makes the cell faster
reaching the threshold and so faster to get excited).

Phases of pace-maker potential

1. phase-1 (slow depolarization phase, prepotential or the slope )
- It starts with the sodium ions leaking into the cells through leaky sodium channels and
cause slow depolarization.
- Then, calcium channels open and raise the membrane potential towards threshold
level of – 40 mV.
- Thus, the initial part of pacemaker potential is due to slow influx of sodium ions and
the later part is due to the slow influx of calcium ions.
2. phase 2: (depolarization)

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- When the threshold level is reached, more Ca+2 channels open causing more Ca +2
influx resulting in a rapid depolarization. Unlike in other tissues, the depolarization in
SA node is mainly due to the influx of calcium ions, rather than sodium ions.
3. phase 3: (repolarization)
- Ca2+ channels close.
- K+ channels open causing efflux of potassium ions. This leads to the development of
more negativity, beyond the level of resting membrane potential (i.e. hyper
repolarization).
- Then, the slow depolarization starts once again, leading to the development of
pacemaker potential, which triggers the next action potential.

Effect of autonomic stimulation on the heart rate

Sympathetic activation, onto the SA node, increases pacemaker rate by increasing the slope of phase
4 so that the pacemaker potential more rapidly reaches the threshold for action potential generation.

Parasympathetic activation, onto the SA node, decreases pacemaker rate by decreasing the slope of
phase 4 of the action potential, thereby increasing the time required to reach threshold.

Conductive system in the heart

Conductive system of the heart is formed by the modified cardiac muscle fibers. These fibers are the
specialized cells, which conduct the impulses rapidly from SA node to the ventricles. This system is
a network of specialized cardiac muscle cells that initiates and distributes electrical impulses. The
actual contraction lags behind the beginning of an electrical impulse (the action potential). The delay
comes from the time it takes for calcium ions to enter the sarcoplasm and activate the contraction
process (i.e. excitation-contraction coupling).

 Components of conductive system

1- The sinoatrial (SA) node
2- The iternodal pathways
3- The atrioventricular (AV) node
4- The AV Bundle (bundle of His)
5- Bundle Branches
6- Purkinje Fibers
 Velocity of impulses at different parts of conductive system
1. Atrial muscle fibers : 0.3 meter/second

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2. Internodal fibers : 1 meter/second

3. AV node : 0.05 meter/second
4. Bundle of His : 0.12 meter/second
5. Purkinje fibers : 4 meter/second
6. Ventricular muscle fibers: 0.5 meter/second.

Thus, the velocity of impulses is maximum in Purkinje fibers and minimum at AV node. The
conducting system includes the following elements:

1- The sinoatrial node (SA node):

This node is located in the posterior wall of the right atrium, near the entrance of the superior vena
cava. The SA node contains pacemaker cells, which establish the heart rate. As a result, the SA node
is also known as the (cardiac pacemaker or the natural pacemaker).

2. The iternodal pathways:

These pathways are located in the atrial walls and they connect the SA node with the AV node. An
action potential travels from the SA node to the AV node spreads to the atrial contractile cells
through gap junctions. The stimulus affects only the atria, because the cardiac fibrous skeleton
isolates the atrial myocardium from the ventricular myocardium.

2- The Atrioventricular (AV) Node:

The relatively large atrioventricular (AV) node sits within the floor of the right atrium near the
opening of the coronary sinus. The impulse slows as it leaves the iternodal pathways and enters the
AV node, because the nodal cells are smaller in diameter than the rest of the conducting cells. In
addition, the connections between AV-nodal cells are less efficient than those between conducting
cells at relaying (passing) the impulse from one cell to another due to less gap junctions. As a result,
the impulse will be delayed upon passing through the AV node. This delay is important because it
allows the atria to contract before the ventricles. Otherwise, contraction of the powerful ventricles
would close the AV valves and prevent blood flow from the atria into the ventricles.

3- Atrioventricular bundle (AV bundle or bundle of His):

It is the only electrical connection between the atria and the ventricles. The AV bundle crosses the
electrically insulating fibrous ring that separates atria and ventricles then, at the upper end of the
ventricular septum; it divides into right and left bundle branches.

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4- Bundle Branches:

Once an impulse enters the AV bundle, it travels to the interventricular septum and enters the right
and left bundle branches. The left bundle branch, which supplies the massive left ventricle, is much
larger than the right bundle branch. Both branches extend toward the apex of the heart, turn, and
spread out deep to the endocardial surface.

5. Purkinje Fibers:
The cells of Purkinje fibers are much larger in diameter than all other cardiac cells; as a result, they
conduct action potentials more quickly than other conducting cells. The Purkinje fibers radiate from
the apex toward the base of the heart. As a result, the ventricles contract in a wave that begins at the
apex and spreads toward the base. The contraction pushes blood toward the base of the heart, into the
aorta and pulmonary trunk.