3111 PHYSİOLOGY
06/11/2019 Physiological Properties of Cardiac
Muscle(Cont.)
CONTENTS:
a. Fast Action Potential(from previous
lecture)
b. Ca-induced Ca-release and
Contraction of Heart
c. Relaxation of Heart
d. Drugs that Affect Cardiac Cells
e. Slow Action Potential
f. Conduction System
g. Previous Questions
Action potential graphics formed by :
A. Ventricle (fast action potential),
B. Sinoatrial nodal cells and
atrioventricular nodal cells ( slow
action potential)
C. Atrium (fast action potential)
Neslihan Dikmenoğlu
Falkmarken
A. Fast Action Potential Summary
• RMP of cardiac muscle is produced by
inward rectifying potassium channels
which close when the cells start to
depolarize.(These channels open again at
the end of repolarization,let outward
movement of potassium and contribute to
the last part of repolarization in the action
potential.)
• Local potential (showed by blue curved line
in the graphicA) is produced by electrical
synapses.
• At about -65 (horizontal line in
graphicA),we reach the threshold of
voltage gated Na channels,which open
quickly and produce depolarization phase
(phase 0) of the action potential.
• At Phase 1(rapid repolarization phase –in
books Phase1 is called early repolarization
so you’d better know these two names),
there is only transient outward movement
of K by transient outward channels.So
there is a short and rapid repolarization at
this phase.
• But during plateau (phase 2), inward
movement of positive charges is equal to
the outward movement of positive charges.
- Outward going ions are K (it’s believed that
they use the transient outward channels
and delayed rectifier K channels- there are
2 types of delayed rectifier K channels:
rapid and slow. But lecturer didn’t go into
more detail.)
- Inward coming ions are mainly Ca. They
come through L-type Ca channels.
Reminder : In the heart we have mainly 2
types of Ca channels :
• L-type (opens late-long lasting) voltage
gated channels
• T-type (opens earlier-transient) voltage
gated channels.
• In fast action potentials, we have mainly long lasting (L-type) voltage gated Ca
channels. Long lasting(L-type) channels open about -30mV and they are especially
prominent at plateau (phase 2).
• So Ca comes into the cell through L-type voltage gated Ca channels at phase 2
(plateau phase).

• After the inward and outward movement of positive ions at phase

2,repolarization occurs at phase 3 of action potential.
• During phase 3,mainly K is sending out through channels which are :
- Transient outward channels
- 2 types of delayed rectifier channels ( rapid and slow )
- Inward rectifier K channels ( towards the end of the repolarization) (That’s the
tricky point lecturer said in first lecture. Even if their names are inward rectifier
channels, they allow movement of K out of the cell a little bit; they help
repolarization and they produce Resting Membrane Potential.)
 Cardiac AP is longer than
the nervous and skeletal
AP, and this mechanism
helps inhibit the tetanic
contraction in cardiac
muscle.

• Na-Ca Exchanger sends Ca out at the RMP(phase4).

• As the cell depolarizes,behaviour of the NCX changes. NCX activity is also
dependent in Ca concentration.
-It’s believed that this exchanger sends Ca to the inside of the cell at
phase 2.
-At the beginning of phase 3, it again starts sending Ca to the outside of the
cell because it’s now trying to relax the muscle.
 B. Ca-induced Ca-release and Contraction of Heart

1. Ca enters the cytoplasm from ECF by L-type voltage gated Ca channels .

2. It moves through the cytoplasm and goes the the sarcoplasmic reticulum(SR).(Surface of SR is
away from the cell membrane so we can not talk about any membrane potential here,there is
no longer electrical activity.)
3. Then the Ca,that comes by electrical activity, triggers the SR to release more Ca by opening
the Ca-gated Ca channels/Ryanodine Receptor.(it’s a type of ligand gated channel)
4. By this way Ca goes out of the SR.

• %20 of Ca comes from outside.

• %80 of Ca comes from SR.(With %20 Ca that comes from outside,%80 Ca release is provided,so
that’s why extracellular Ca is important for heart.)
• So,internal and external calciums come together and then contraction happens.
• Ca gated-Ca channels are far away from the cell membrane so they are nothing to do with
membrane potential.

• Ca gated-Ca channels = ryanodine receptors(RyR).

• The opening of RyR that founds in the heart is different from that in
the skeletal muscle.
-Skeletal muscle RyR’s, are mechanically-gated and activated by
dihydropyridine receptors but the ones that are found in the heart
muscle are ligand-gated.
 C. Relaxation of Heart

• For the cardiac muscle relaxation :

1. %80 Ca that comes from SR,goes back to the SR with SERCA (Sarcoplasmic reticulum Ca
ATPase)
2. %20 Ca send back to the ECF by :
- Plasma membrane Ca-ATPase
- Na-Ca Exchanger (towards the end of the plateau, it starts the sending Ca to outside.)

• There are 2 stimuli for the NCX :

1. Ca level/ When the internal Ca level increases,it starts to sending it out.
2. Membrane potential/ When the level of the membrane potential changes , NCX also
changes inward or outward. ( At the phase 4 of ventricular action potential,NCX sends
the Ca out but as the cell depolarizes it sends Ca in.)
D. Drugs that Affect Cardiac Cells

• Na/K ATPase 2 K in,3 Na out.(primary active transport)

• Na/Ca Exchanger 3 Na in,1 Ca out.( secondary active transport,using the
concentration gradient of Na that produces by Na/K ATPase.)
• Digitalis drugs blocks the Na/K ATPase(These drugs don’t have a direct effect on
NCX).When this protein is blocked :
1. Sodiums can not be excreted to outside.
2. So ,they can not be taken by NCX and NCX can’t send Ca out.

Digitalis drugs indirectly prevent the Ca movement to out of the cell.

-If calcium stays in the cell,it increases the force of contraction.

• There is also Ca-channel blocking drugs and they prevent the entry of the calcium.
• By this way,they decrease the contraction force of heart but the main reason that we use
these drugs is their function in decreasing the contraction of blood vessels.(If there is a
high blood pressure in aorta,heart is going to have a problem.If we relax the aorta then
heart can pump the blood easily.)

E. Slow Action Potential

 • In the pacemaker
cells,change in the
potential (1) is called as
prepotential or diastolic
depolarization.
- Diastole is the filling of
the ventricles.
- With the atrial
systole,ventricular
diastole is completed.

• Factors that produce the prepotential :

1. Closure of K channels
2. Opening of funny Na channels by hyperpolarization
-This opening produces funny current/ If
3. Opening of T-type voltage gated Ca channels. (There are also some L-type Ca channel
found in SA node which opens earlier. That’s why we say when the sympathetic system
increases heart rate, it effects L-type channels.)

• After prepotential , there is threshold of L-type Ca channels.

 • If you want to increase
heart rate,you should reach
the threshold earlier
(dashed blue line)
• The way of increasing the
heart rate is playing with
the prepotential.
- (Kalbin hızını artırmak
istiyosanız,prepotensiyeli
hızlandırıp eşik değere
çabuk ulaşmanız
gerekiyor.Bunu sağlamak
için prepotensiyel
oluşumunu sağlayan
faktörlerden birini
değiştirmeniz lazım.)

F. Conduction System

• At time zero,an action potential starts at the SA node.

• Because of AV node produces a little bit slower action potential (reach the threshold
lately),starting point of action potential is SA node.
• But in some diseases,if SA node stops there are 2 possibilities :
- You die or,
- AV node takes over
• If AV node stops,again there are 2 possibilities :
- You die or,
- Purkinje fibers take over.
1. Action potential starts at the SA node at the time 0.
2. Electrical activity spreads to the right atrium by interatrial bundles and passes to the
left atrium.
3. Then electrical activity reaches to the AV node at 0.03rd sec. and at 0.09th sec. all
atria depolarization is completed.(The first cell that depolarizes stays depolarized for
200 milisec. at the plateau.)
4. Action potential comes to the AV node at 0.03rd sec. but leaves here at 0.16th sec.The
resason of this waiting is :
- Action potential does not move to the ventricles until the atrial contraction and
relaxation is complete.(atrial contraction completes the filling of ventricles.)

• How AV node prevents the passage of action potential to the ventricle while atria
contract ?
i. Cells in the AV node are small that's why they have a bigger resistance to the passage
of electrical activity
ii. In AV node there are smaller amount of gap junctions.(Gap junctions let the passage
of electicity from one cell to another.)
- So ,smaller size of the cells and smaller number of gap junctions at the AV node
cause the passage of electrical activity into the ventricle is delayed.By this way atria
contracts before the ventricles.

5. After AV node,electrical activity spreads in the septum downward until the

endocardium .
6. Moves along the endocardium in 0.03 sec.(at 0.19th sec.)
7. From endocardium,it moves to myocardium and epicardium in 0.03 sec (at 0.21st sec.)
 • Heart muscle forms a functional syncytium,works as a one piece.
- The electrical junctions help the spread of action potentials very quickly so that all of the
cells contract at the same time.

• The heart rate is :

a) 60-100 beats / min. when the SA node is working.
b) 40-60 beats / min. when the AV node is working.
c) … <40 beats / min. when purkinje fibers are working.

G. Previous Questions

1. I. transient outward potassium channels type 1 and 2

II. delayed rectifier potassium channels
III. L-type calcium channels
IV. T-type calcium channels
V. inward rectifying potassium channels In the ventricular muscle
Which of the above ion channels contribute to the plateau?

A) I, II and V B) II,III and IV C) II, IV and V D) I, II and III E) III, IV ve V

Answer : D
During plateau (phase 2):
- Outward going ions are K(by transient
outward channels and delayed rectifier
channels)
- Inward coming ions are mainly Ca(by L-type
Ca channels)
2. Choose the incorrect statement about the Na+-Ca+2 exchanger in the membrane of heart
muscle cells.
A) It works as a secondary transport system dependent on Na+-K+ ATPase pump.
B) It brings 3 sodium ions into the cell.
C) It brings 1 calcium ion out of the cell
D) It is blocked directly by digitalis
E) It ends the contraction.

Answer : D
- Digitalis drugs blocks the Na/K
ATPase(These drugs don’t have a direct
effect on NCX).

3. Which statement about the atrioventricular node is incorrect?

A) It is the only passage way for the electric impulse from the atria into the ventricles.
B) It delays the passage of the electrical impulse to the ventricles.
C) It conducts only in one direction. Impulses from the ventricles cannot pass into the atria.
D) It provides time for the atria to contract before the ventricles.
E) When it becomes a pacemaker, the heart beat at a rate slower than 40 beats/minute.

Answer : E
• The heart rate is :
a) 60-100 beats / min. when the SA node
is working.
b) 40-60 beats / min. when the AV node
is working.
c) … <40 beats / min. when purkinje
fibers are working
4. What produces phase 4 (resting membrane potential) of the fast action potentials in the heart
muscle cells?
A) Inward rectifying K+ channels
B) voltage gated Na+ channels
C) L-type voltage gated Ca+2 channels
D) Transient outward K+ current
E) delayed rectifier K+ channels

Answer : A

5. What produces phase 0 (depolarization) of the fast action potentials in the heart?
A) İnward rectifying K+ channels
B) Voltage gated Na+ channels
C) L-type voltage gated Ca+2 channels
D) T-type voltage gated Ca+2 channels
E) delayed rectifier K+ channels

Answer : B
6. Choose the INcorrect statement about the actions of calcium ions in the ventricular muscle cells.
A) During contraction heart muscle receives calcium only from the extracellular fluid.
B) Calcium enters the cytoplasm from the extracellular fluid through L-type voltage gated Ca
channels.
C) Calcium enters the cytoplasm during the plateau phase of the action potential
D) Calcium is sent back to the extracellular fluid by Ca-ATPase
E) Calcium is sent back to the extracellular fluid by Na-Ca exchanger.

Answer : A
• %20 of Ca comes from outside.
• %80 of Ca comes from SR.

7. Choose the INcorrect sentence about the fast action potential in the heart cells.
A) Phase 4 (resting membrane potential) is produced by inward rectifying K channels.
B) Phase 0 is produced by voltage gated fast Na channels
C) Phase 1 is produced by transient outward K current
D) During phase 2 K moves inward as Ca moves outward and the membrane potential is kept fairly
constant.
E) Delayed rectifier K channels, transient outward K current and finally inward rectifying K
channels contribute to phase 3.

Answer : D

8. I. voltage gated sodium channels

II. inward rectifying potassium channels
III. transient outward potassium channels
IV. funny (hyperpolarization induced) Na
channels
V. T type Calcium channels
Which of the channels and ions above is/are responsible for the formation of prepotential at
the nodal cells?
A) I
B) I and II
C) II and III
D) III and IV
E) IV and V

Answer : E

S. Emre METİN