Download Impulse Generation

Impulse Generation
2-May-17
CVS Impulse generation
1
Impulse Generation


The heart is
composed of three
types of muscles
Atria & ventricles


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CVS Impulse generation
Form the working
myocardium
They do the
mechanical work of
pumping
2
Impulse Generation

The specialized
tissues

Excitatory &
conducting tissues




2-May-17
CVS Impulse generation
Sino atrial node
Atrio-ventricular
node
Bundle of his
Purkinje fibers
3
Myocardium

Myocardial fibers


Excitable tissue
Have a resting membrane potential


Mechanism of genesis of RMP


Between –60 to –90 mv
Similar to that in skeletal muscles
Cardiac muscle respond

To supra threshold stimuli by


2-May-17
Generating an action potential
Capable of propagating it
CVS Impulse generation
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Myocardium

Excitation arising in atrium or
ventricles


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Spread over the unexcited tissue
Works as a syncytium
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Cardiac Action Potential

+20 mv
1
General properties of
cardiac AP

2
0 mv

3
Special permeability
differences

0
Similar to that of nerve
& skeletal muscle
Lead to difference in
shape of cardiac AP
4
- 85 mv
0 = depolarization
2-May-17
1
= initial
repolarization
2
Plateau phase
3
repolarization
CVS Impulse generation
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Cardiac Action Potential

+20 mv
1
In the cardiac cells after
the initial spike

2
0 mv
3
0

Membrane remains
deoplarized for
 About 0.2 sec in
atria
 About 0.3 sec in
ventricles
Exhibiting a plateau
4
- 85 mv
0 = depolarization
2-May-17
1
= initial
repolarization
2
Plateau phase
3
repolarization
CVS Impulse generation
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Cardiac Action Potential

+20 mv
Depolarization

1
2

0 mv
3

0
4
- 85 mv
Due to  in Na+
conductance
Opening of fast
sodium channels
Initial
repolarization

Due to closure of
sodium channels
0 = depolarization
2-May-17
1
= initial
repolarization
2
Plateau phase
3
repolarization
CVS Impulse generation
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Cardiac Action Potential

+20 mv
The plateau phase

1
2
0 mv
3
0

4
- 85 mv
0 = depolarization
2-May-17
1
= initial
repolarization
2
Plateau phase
3
repolarization
CVS Impulse generation
Due to slow prolonged
opening of
 Voltage gated Ca++
channels
 Become activated at
potential of –30 to –
40 mv
Also known as
 Slow calcium
channels
 Calcium – sodium
channels
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Cardiac Action Potential

+20 mv
1
2
0 mv
3
0
Large amount of
Ca++ & Na+
 Flow through
these channels
 Prolong the
period of plateau
phase
4
- 85 mv
0 = depolarization
2-May-17
1
= initial
repolarization
2
Plateau phase
3
repolarization
CVS Impulse generation
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Cardiac Action Potential

+20 mv
1
2
0 mv
3
0
At the end of
plateau phase
 Slow calciumsodium channels
close
 Influx of Ca++ &
Na+ ceases
4
- 85 mv
0 = depolarization
2-May-17
1
= initial
repolarization
2
Plateau phase
3
repolarization
CVS Impulse generation
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Cardiac Action Potential

+20 mv
1
2
0 mv
Permeability of
cardiac muscle to
K+ increases

3

0
4
- 85 mv
0 = depolarization
2-May-17
1
= initial
repolarization
2
Plateau phase
3
repolarization
CVS Impulse generation
Efflux of K+
Return the
membrane
potential to its
resting value
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Refractory Period

+20 mv
1
During the action
potential

2
0 mv
3

0
4
- 85 mv
Absolute
refractory period
0.25 – 0.3 sec
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Cardiac muscle is
refractory to restimulation
Cardiac impulse
cannot re-excite an
already excited area
Relative refractory
period 0.05 sec
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Refractory Period

+20 mv
1
2
Normal
refractory period

0 mv
3

0
4
- 85 mv
Absolute
refractory period
0.25 – 0.3 sec
2-May-17
0.25 to 0.3
seconds
Approx equal to
duration of action
potential
Relative refractory
period 0.05 sec
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Refractory Period

+20 mv
1
Relative refractory
period

2
0 mv

During this period

3
0.05 seconds
0

Muscle is more
difficult to excite
But can be excited
4
- 85 mv
Absolute
refractory period
0.25 – 0.3 sec
2-May-17
Relative refractory
period 0.05 sec
CVS Impulse generation
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Refractory Period

+20 mv
1
Refractory period

2
0 mv
3
Is due to
inactivation of
sodium channels

0
During prolonged
depolarization
4
- 85 mv
Absolute
refractory period
0.25 – 0.3 sec
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Relative refractory
period 0.05 sec
CVS Impulse generation
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Refractory Period

+20 mv
1
Not until the
membrane

2
0 mv

3
Has repolarized to –
50 to –60 mv
Does sodium
channels recover
0
4
- 85 mv
Absolute
refractory period
0.25 – 0.3 sec
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Relative refractory
period 0.05 sec
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Refractory Period

+20 mv
The cells in SAN

1
2
0 mv
Have transmembrane potential
of

3

0
- 85 mv
Absolute
refractory period
0.25 – 0.3 sec
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SAN cells
membrane

4
-55 to –60 mv
between discharges
Naturally leaky to
Na+
Relative refractory
period 0.05 sec
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Pacemaker Potential

+20 mv
Na+ tend to leak
into the cell

0 mv

Transient (T) Ca++
channels open

-50 mv
Responsible for the
initial phase of pace
maker potential
Entry of Ca++

-60 mv
Completes the prepotential phase
Pacemaker
potential
Ca++
Na+
Ca++
Na+
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CVS Impulse generation
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Pacemaker Potential

+20 mv
0 mv
The long lasting (L)
Ca++ channels then
open


Ca++
More Ca++ influx
Which produces the
impulse
-50 mv
-60 mv
Pacemaker
potential
Ca++
Na+
Ca++
Na
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+
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Pacemaker Potential
K+
+20 mv
K+

At the peak of each
impulse

0 mv


Ca++
K+ ion channels open
Efflux of K+ ions
Brings about
repolarization
-50 mv
-60 mv
Pacemaker
potential
Ca++
Na+
Ca++
Na
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+
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Pacemaker Potential
K+
+20 mv
K+

The potassium
channels then close

0 mv

Ca++
Na+ ions leak into the
cell
Causing the initial
phase of prepotential
-50 mv
-60 mv
Pacemaker
potential
Ca++
Na+
Ca++
Na
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+
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Pacemaker Potential
K+
+20 mv
K+

Calcium ions
channels then

0 mv


Ca++
Open
Calcium influx
Completing another
deplorization
-50 mv
-60 mv
Pacemaker
potential
Ca++
Na+
Ca++
Na
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+
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Spread of Excitation

Depolarization
initiated in SAN



Atria depolarization

2-May-17
Spread radially
through atria
Then converge to
AVN
CVS Impulse generation
Complete in 0.1
second
24
Spread of Excitation

Conduction in AVN is
slow

Cause 0.1 sec delay


Then the excitation



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AVNodal delay
CVS Impulse generation
Spread to bundle of His
Then to purkinje fibers
To the ventricular
myocardium
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Spread of Excitation

The conducting system
is such that


Gives time for


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Cardiac impulse will not
travel from atria to
ventricle too rapidly
CVS Impulse generation
Atrial emptying before
Ventricle contraction
begins
26
Control of Excitation in Heart

The pacemaker cells



Why does the SAN


SANode, AVNode, Purkinje cell
All exhibit rythmicity
Become the dominant pacemaker
Why not

2-May-17
The AVNode or Purkinje fibers dominate
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Control of Excitation

The normal rate of discharge from
these cells



2-May-17
SAN = 70 to 80 per minute
AVN = 40 to 60 per minute
Purkinje fibers = 15 to 40 per minute
CVS Impulse generation
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Control of Excitation

In all these cells

To change from “resting” to threshold potential


Thus threshold is reached much faster

2-May-17
Require a change of 20 to 25 mv
In SAN than in Purkinje fibers
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Factors Affecting the Rate of
Pacemaker

+20 mv
0
Rate established by
pacemaker cells
depend on

c
- 40 mv
- 60 mv
b
d
f
Threshold
pot
Time required for
membrane pot


a
To change from
resting to threshold
For generation of AP
e
Normal
time
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CVS Impulse generation
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Factors Affecting the Rate of
Pacemaker

+20 mv
0
Change in heart
rate will be
mediated by

c
- 40 mv
- 60 mv
b
d
f
Threshold
pot


a
Magnitude of initial
“RMP”
Rate of
depolarization
Threshold value
e
Normal
time
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CVS Impulse generation
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Factors Affecting the Rate of
Pacemaker

+20 mv
If the “RMP” becomes
more negative


0
It takes longer to reach
threshold

c
- 40 mv
- 60 mv
b
d
f
Threshold
pot

From (e to f) as
compared from (a to b)
Thus the heart rate

a
Shift from (a to e)
Decreases
e
Normal
time
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CVS Impulse generation
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Factors Affecting the Rate of
Pacemaker

+20 mv
0
An increase in the
rate of
depolarization

c
- 40 mv
- 60 mv

b
d
f
Threshold
pot


a
e
It takes shorter to
reach threshold
From (a to c)
Compared from (a to
b)
The heart rate will
increase
Normal
time
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CVS Impulse generation
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Factors Affecting the Rate of
Pacemaker

+20 mv
A shift of threshold
potential

0

c
- 40 mv
- 60 mv
b
d
f
Threshold
pot
To a more negative
value
Will cause an
increase in heart rate
a
e
Normal
time
2-May-17
CVS Impulse generation
34
Cardiotonic Agents

Chronotropic agents

Alter the excitability of



Positive chronotropic agents


Lead to increase in heart rate
Negative chronotropic agents

2-May-17
Pacemaker
Conducting system
Lead to decrease in the heart rate
CVS Impulse generation
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Cardiotonic Agents

Inotropic agents


Positive inotropic agents


Affect the contractility of the cardiac
muscles
Lead to increase in contraction
Negative inotropic agents

2-May-17
Lead to decrease in contraction
CVS Impulse generation
36
Effects of Ions

Calcium ions


Have a positive inotropic effect
 In ECF Ca++ concentration leads to

 In force of contraction of cardiac muscle


More Ca++ available for troponin
 In ECF Ca++ concentration reduces

2-May-17
Myocardial force of contraction
CVS Impulse generation
37
Effects of Ions

Calcium ions


Have a chronotropic effect too
 In ECF Ca++ concentration

2-May-17
Slow the heart rate
 By elevating the excitation threshold
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Effects of Ions

 In ECF Ca++ concentration


Increases the heart rate
 Due to increase in rate of diastolic
depolarization
Purkinje cells are more sensitive to
Ca++

2-May-17
Leads to development of ectopic foci
CVS Impulse generation
39
Effects of Ions

Sodium ions


Have little effects under normal conditions
A decrease in ECF Na+ concentration

Slows the heart


Severe reduction (10%) in Na+ concentration

2-May-17
Decrease in amplitude of AP
Leads to complete loss of excitability
CVS Impulse generation
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Effects of Ions
 Potassium

ions
An increase in ECF K+ concentration
 Dilated
heart which is flaccid
 Heart rate falls
 Impaired conduction in AVNode
 Lead to atrial block
2-May-17
CVS Impulse generation
41
Effects of Ions
 An
increase in ECF K+
concentration

Causes partial depolarization



Shortens duration of AP
Decreases amplitude & intensity of AP
Hence the contraction of heart

2-May-17
Becomes progressively weaker
CVS Impulse generation
42
Effects of Autonomic Nervous
System

Sympathetic stimulation increases




2-May-17
Rate of sinus node discharge
Rate of conduction
Level of excitability of myocardium
Force of contraction of myocardium
CVS Impulse generation
43
Nor adrenalin

Nor adrenalin increases



2-May-17
The rate of SAN cells depolarization
The rate of spontaneous discharge
Heart rate
CVS Impulse generation
44
Effect of Nor Adrenalin
Ca++
Nor adrenalin

1 receptor
Adenyl cyclase
Nor adrenalin acts
on 1 receptors

GS protein

ATP
cAMP
Increase in cAMP
Activated protein
kinase A
Protein
Kinase
Ca++
Ca++
Sarcoplasmic
Ret
Troponin
2-May-17
CVS Impulse generation
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Effect of Nor Adrenalin
Ca++
Nor adrenalin

1 receptor
Adenyl cyclase
Protein Kinase A
facillitates

GS protein
ATP
cAMP


Protein
Kinase
Ca++
Ca++
Opens long lasting
Ca++ channels
Influx of Ca++ into
myocardial cell
Leads to increase in
strength of
contraction
Sarcoplasmic
Ret
Troponin
2-May-17
CVS Impulse generation
46
Parasympathetic

Parasympathetic stimulation


Causes release of Acetylcholine
This causes a decrease


Heart rate
Excitability of AVN

2-May-17
Slows transmission of impulses to ventricles
CVS Impulse generation
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Parasympathetic

Very strong stimulation


Can stop SAN discharge
Block AVN transmission
Ventricle can stop contraction
 Vagal escape


2-May-17
Ectopic pacemaker from Purkinje fibers
take over
CVS Impulse generation
48
Parasympathetic

Acetylcholine


Activate M2 (muscarinic) receptors
Through G-protein



2-May-17
Open special K+ channels
Efflux of K+
Hyperpolarization
CVS Impulse generation
49
Parasympathetic

Activation of M2 recptors also

Decrease cAMP concentration in cell


Rate of diastolic depolarization is retarded


2-May-17
Slows opening of Ca++ channels
It takes longer to reach threshold
Heart rate is slowed
CVS Impulse generation
50
Cardiac Glycosides

2Na+

1 Ca++

2Na+
Na+/K+
ATPase
pump
2 K+
3 Na+
2-May-17
1 Ca++
Digitalis increase
cardiac contractility
Inhibits sodiumpotassium ATPase
In the heart
myocardium

Ca++/Na++
antiport
pump
CVS Impulse generation
There is an antiport
transport mechanism
51
Cardiac Glycosides

2Na+
1 Ca++
Cell membrane
exchange ICF
calcium for ECF
sodium

2Na+
Na+/K+
ATPase
pump
2 K+
3 Na+
2-May-17
1 Ca++
Ca++/Na++
antiport
pump

1 Ca++ for 2 Na+
The rate of
exchange

CVS Impulse generation
Proportional to
concentration of Na+
in ICF
52
Cardiac Glycosides

2Na+
Inhibition of Na+ K+ pump

1 Ca++
2Na+
Na+/K+
ATPase
pump
2 K+
3 Na+
2-May-17
1 Ca++

Ca++/Na++
antiport
pump
CVS Impulse generation
Leads to increase in
Na+ concentration in
ICF
This interferes with
antiport mechanism
53
Cardiac Glycosides

2Na+
1 Ca++
2Na+
Na+/K+
ATPase
pump

1 Ca++
2 K+
3 Na+
2-May-17
There is increase in
ca++ concentration
in ICF
Followed by  force
of contraction of
myocardial cells
Ca++/Na++
antiport
pump
CVS Impulse generation
54