LIU Chuan Yong
刘传勇
Institute of Physiology
Medical School of SDU
Tel 88381175 (lab)
88382098 (office)
Email: liucy@sdu.edu.cn
Website: www.physiology.sdu.edu.cn
1
Section 2
Electrophysiology of
the Heart
2
CARDIAC
ELECTROPHYSIOLOGY
3
Two kinds of cardiac cells
1, The working cells.
Special property:
contractility
4
2, Special conduction system including the
Sinoatrial node,
Atrioventricular
node,
Atrioventricular
bundle (bundle of
His),
and Purkinje
system.
Special property:
automaticity 5
I. Transmembrane Potentials of
Myocardial Cells
6
Ions and Cells
Na+
K+
Ca+2
Mg+2
ClHCO3SO4-2
Phosphates
pH
Extracellular
fluid
Intracellular
fluid
140 mM
4 mM
2.4 mM
1.2 mM
103 mM
28 mM
1 mM
4 mM
7.4
10 mM
140 mM
~50 nM
4 mM
58 mM
10 mM
2 mM
75 mM
7.0
Na+
ATP
K+
A -Cell
0XmV
mV
Na+
Cl-
Cl-
K+
Na+
Cl-
Cl-
K+
ClNa+
K+
Na+
K+
Cl-
Cl-
K+
K+
Na+
Cl-
Cl-
Cl-
K+
ClCl-
Cl-
Na+
Cl-
Na+
Cl-
K+
K+
Cl-
Na+
Lipid bilayer
membrane
Equilibrium
 The process of ions diffusing and changing
the membrane voltage will continue
 until the membrane potential attains a value
sufficient to balance the ion concentration
gradient.
 At this point the ion will be “in equilibrium”.
 What is this potential?
The Nernst Potential
An ion will be in equilibrium when the membrane
potential is:
RT X o
ln
zF X i
where [X]o and [X]i are the external and internal
concentrations of the ion; R, T, and F are thermodynamic
constants such that (at 37 °C):
VX  61 log
X o mV
X i
The Nernst
Potential
For Example...
 Typically, [K]o = 4 mM and [K]i = 140 mM
 so VK = 61*log(4/140) = - 94 mV
 i.e. a cell with these normal K concentrations and ONLY a Kselective ion channel will have a membrane potential of -94 mV
 Likewise, [Na]o = 140 mM and [Na]i = 10 mM
 so VNa = 61*log(140/10) = + 70 mV
 i.e. a cell with these normal Na concentrations and ONLY a Naselective ion channel will have a membrane potential of +70 mV
ACTION POTENTIALS FROM
DIFFERENT AREAS OF THE HEART
Fast and Slow Response
ATRIUM
VENTRICLE
0
mv
mv
0
-90mv
-90mv
SA NODE
mv
0
-80mv
12
time
ELECTROPHYSIOLOGY OF THE
FAST VENTRICULAR MUSCLE
+20
AMP
1
2
0
0
3
Cardiac Cell
4
-90
0
300
t (msec)
13
General description
Phase 0: rapid
depolarization, 1-2ms
Resting potential: -90mv
Action Potential
+20
Phase 1: early rapid
repoarization, 10 ms
1
2
Phase 2: plateau, slow
repolarization, the
potential is around 0
mv. 100 – 150ms
0
0
3
4
-90
0
300
t (msec)
Phase 3, late rapid
repolarization. 100 –
150 ms
Phase 4 resting potentials
14
Ion Channels in Working
Muscle
 Essentially same in atrial and
ventricular muscle
 Best understood in ventricular
cells
15
Ion Channels in Ventricular
Cells




Voltage-gated Na+ channels
Inward rectifier K+ channels
L-type Ca2+ channels
Several Voltage-gated K+ channels
16
Cardiac
+
Na
Channels
 Almost identical to nerve Na+ channels
(structurally and functionally)
 very fast opening (as in nerve)
 has inactivation state (as in nerve)
 NOT Tetrodotoxin sensitive
 Expressed only in non nodal tissue
 Responsible for initiating and propagating
the action potential in non nodal cells
17
+20
1
2
0
0
3
4
-90
0
300
t (msec)
18
Inward Rectifier (Ik1)
Structure
Note: No “voltage sensor”
P-Region
Extracellular
Fluid
M1
M2
membrane
Inside
H2N
HO2C
19
Inward Rectifier
Channels
Current
0
Ek
-120
-100
-80
-60
-40
-20
Vm (mV)
0
20
40
60
20
Inward Rectification
K+
K+
Mg2+
Mg2+
K+
K+
K+
K+
-80
-30 mV
mV
K+
21
Intracellular Solution
Extracellular solution
K+
K+
Inward Rectifier
Channels
Current
0
Ek
-120
-100
-80
-60
-40
-20
Vm (mV)
0
20
40
60
22
Role for Inward Rectifier
 Expressed primarily in non nodal tissues
 Sets resting potential in atrial and
ventricular muscle
 Contributes to the late phase of action
potential repolarization in non nodal cells
23
+20
1
2
0
0
3
4
-90
0
300
t (msec)
24
Inactivating K channels (ITO)
“Ultra-rapid” K channels (IKur)
“Rapid” K channels (IKr)
“Slow” K channels (IKs)
Cardiac Voltagegated K Channels
 All structurally similar to nerve K+ channels
 ITO is an inactivating K+ channel- rapid
repolarization to the plateau
 IKur functions like nerve K+ channel- fights
with Ca to maintain plateau
 IKr, IKs structurally and functionally complex
25
Cardiac
2+
Ca
Channels
 L-type
 Structurally rather similar to Na channels
 Some functional similarity to Na
channels
 depolarization opens Ca2+ channels
 Functionally different than Na channels
 slower to open
 very slow, rather incomplete inactivation
 generates much less current flow
26
Role of Cardiac Ca2+
Channels
 Nodal cells
 initiate and propagate action potentialsSLOW
 Non nodal cells
 controls action potential duration
 contraction
27
Ca2+CHANNEL BLOCKERS AND
THE CARDIAC CELL ACTION
POTENTIAL
CONTROL
FORCE
30
10
DILTIAZEM 地尔硫卓
10 µMol/L
30 µMol/L
10
CONTROL
30
28
TIME
Ion Channels in Atrial Cells
 Same as for ventricular cells
 Less pronounced plateau due to different
balance of voltage-gated Ca2+ and K
channels
ATRIUM
-90mv
0
mv
mv
0
VENTRICLE
-90mv
29
OVERVIEW OF SPECIFIC EVENTS
IN THE VENTRICULAR ACTION
POTENTIAL
30
Activation & Fast Inactivation
31
PHASE 0 OF THE FAST FIBER
ACTION POTENTIAL
Na+
Na+
m
A
-90mv
B
h
-65mv
m
m
h
Na+
Na+
m
C
0mv
Chemical
Gradient
Electrical
Gradient
m
D
h
+20mv
h
Na+
m
E
+30mv
h
32
Ion Channels in Ventricular
Muscle
Ventricular muscle
membrane potential (mV)
Inactivating K channels (ITO)
“Ultra-rapid” K channels (IKur)
“Rapid” K channels (IKr)
0
Voltage-gated
Na Channels
“Slow” K channels (IKs)
Voltage-gated
Ca Channels
-50
IK1
200 msec
33
Ion Channels in Ventricular
Muscle
Current
Na Current
Ca Current
IK1
ITO
IKur
IKr
IKs
34
2. Transmembrane
Potential of Rhythmic
Cells
35
Ion Channels in Purkinje Fibers
 At phase 4, the
membrane
potential does not
maintain at a level,
 but depolarizes
automatically –
the automaticity

(Phase 0 – 3) Same as for ventricular cells

(Phase 4) Plus a very small amount of If
(pacemaker) channels
36


Activated by negative potential (at about -60 mv
during Phase 3)
37
+
Not particularly selective: allows both Na and K+
The SA node cell
 Maximal repolarization
(diastole) potential, –70mv
 Low amplitude and long
duration of phase 0. It is
not so sharp as ventricle
cell and Purkinje cell.
 No phase 1 and 2
 Comparatively fast
spontaneous depolarization
at phase 4
A, Cardiac ventricular cell
38
B, Sinoatrial node cell
SA node membrane potential (mV)
SA Node Action Potential
Voltage-gated Ca+2 channels
Voltage-gated K+ channels
0
No inward-rectifier
K+ channels
-50
If or pacemaker channels
200 msec
39
SA Node Cells
Current
Ca Current
K currents
If
(pacemaker current)
40
CAUSES OF THE PACEMAKER
POTENTIAL
if
iCa
K+
iK
Na+
Ca++
OUT
IN
41
LOOKING AT THE
PACEMAKER CURRENTS
voltage
iK
if
ionic currents
iCa
42
AV node membrane potential (mV)
AV Node Action Potentials



0
SA node


-50
Similar to SA node
Latent pacemaker
Slow, Ca+2-dependent
upstroke
Slow conduction (delay)
K+-dependent
repolarization
AV node
200 msec
43
Fast and slow response, rhythmic
and non-rhythmic cardiac cells
 Fast response, non –rhythmic
cells: working cells
 Fast response, rhythmic cells:
cells in special conduction
system of A-V bundle and
Purkinje network.
 Slow response, non-rhythmic
cells: cells in nodal area
 Slow response rhythmic cells:
S-Anode, atrionodal area
(AN), nodal –His (NH)cells
44
II Electrical Properties of
Cardiac Cells
Excitability, Conductivity and
Automaticity
45
1. Excitability of Cardiac Muscle
46
(1) Refractory Period
 Absolute Refractory Period – regardless of the strength of a
stimulus, the cell cannot be depolarized.
Transmembrane Potential
 Relative Refractory Period – stronger than normal stimulus can
induce depolarization.
+25
0
-25
-50
RRP
1
2
0
3
ARP
4
-75
-100
-125
0
0.1
0.2
Time (msec)
0.3
47
Refractory Period
 Absolute Refractory Period (ARC):
Cardiac muscle cell completely
insensitive to further stimulation
 Relative Refractory Period (RRC): Cell
exhibits reduced sensitivity to additional
stimulation
48
Na+ Channel Conformations
Closed
Open
Inactivated
Outside
IFM
Inside
IFM
IFM
Non-conducting
conformation(s)
Conducting
conformation
Another Non-conducting
conformation
(at negative potentials)
(shortly after more
depolarized potentials)
(a while after more
49
depolarized potentials)
Refractory Period
 The plateau phase of the
cardiac cell AP increases
the duration of the AP to
300 msec,
 The refractory period of
cardiac cells is long (250
msec).
 compared to 1-5 msec in
neurons and skeletal muscle
fibers.
50
Refractory Period
 Long refractory
period prevents
tetanic contractions
 systole and diastole
occur alternately.
 It is very important
for pumping blood
to arteries.
51
Comparison of refractory period and summation
in cardiac and skeletal muscle fibers
52
Supranormal period:
 The cells can be restimulated and
the threshold is actually lower
than normal.
 Occurs early in phase 4 and is
usually accompanied by positive
after-potentials as some potassium
channels close.
 Can be source of reentrant
arrhythmias especially when
phase 3 is delayed as in long Q-T
syndrome
Absolute
S.N.
Rel
53
54
Skeletal Vs. Cardiac
muscle contraction
Impulse generation: Intrinsic in cardiac
muscle, extrinsic in skeletal muscle
Plateau phase: Present in cardiac muscle,
absent in skeletal muscle
Refractory period: long in cardiac muscle,
shorter in skeletal muscle
Summation: Impossible in cardiac muscle,
possible in skeletal muscle
55
2)
Premature excitation,
premature contraction
and compensatory pause
56
Extra-stimulus
premature
excitation
premature
contraction

compensatory
pause
57
2. Automaticity (Autorhythmicity)
58
Automaticity (Autorhythmicity)
 Some tissues or cells have the ability to
produce spontaneous rhythmic excitation
without external stimulus.
 Different intrinsic rhythm of rhythmic
cells
 Purkinje fiber, 15 – 40 /min
 Atrioventricular node 40 – 60 /min
 Sinoatrial node 90 – 100 /min
 normal pacemarker
 latent pacemarker
 ectopic pacemarker
59
Automaticity (Autorhythmicity)
 The mechanism that SA node
controls the hearts rhythm (acts as
pacemaker) rather than the AV
node and Purkinje fiber
 The capture effect
 Overdrive suppression
60
(3) Factors determining automaticity
 Depolarization rate
of phase 4
 Threshold
potential
 The maximal
repolarization
potential
61
3. Conductivity
62
(1) Pathways and characteristics
of conduction in heart
63
Conducting System of Heart
64
THE CONDUCTION SYSTEM OF THE HEART
65
Flow of Cardiac
Electrical Activity
(Action Potentials)
SA node
Pacing (sets heart rate)
Atrial Muscle
0.4m/s
AV node
0.02 m/s Delay
Purkinje System
4m/s Rapid, uniform spread
Ventricular
Muscle
1m/s
66
characteristics of conduction in heart
Delay in transmission at the A-V node (150 –200
ms) – sequence of the atrial and ventricular
contraction – physiological importance
Rapid transmission of impulses in the Purkinje
system – synchronize contraction of entire
ventricles – physiological importance
67
(2) Factors determining conductivity
 Anatomical factors
 Physiological factors
68
Anatomical factors
 A.Gap junction between working cells
 functional atrial and ventricular syncytium
69
70
Multi-cellular
Organization
= Gap Junction Channel
71
Anatomical factors
 A. Gap junction between working
cells and functional atrial and
ventricular syncytium
 B. Diameter of the cardiac cell –
conductive resistance – conductivity
72
Physiological factors
A. Slope of depolarization and amplitude of
phase 0
 Fast and slow response cells
B. Excitability of the adjacent unexcited
membrane
73
III. Neural and humoral control of the
cardiac function
1. Vagus nerve and acetylcholine (Ach)
Vagus nerve :
 release Ach from postganglionic fiber
 M receptor on cardiac cells
 K+ channel permeability increase
 but Ca 2+ channel permeability decrease
74
ACh on Atrial Action
Potential
(  ) K+ Conductance
(Efflux)
0 mv
- 90mv
Time
75
1) K+ channel permeability increase
resting potential (maximal diastole potential)
more negative
 excitability decrease
76
Ion Channels in Ventricular
Muscle
Ventricular muscle
membrane potential (mV)
Inactivating K channels (ITO)
“Ultra-rapid” K channels (IKur)
“Rapid” K channels (IKr)
0
Voltage-gated
Na Channels
“Slow” K channels (IKs)
Voltage-gated
Ca Channels
-50
IK1
200 msec
77
2) On SA node cells,
K+ channel permeability increase
the depolarization velocity at phase 4 decrease
+ maximal diastole potential more negative
 automaticity decrease
 heart rate decrease
 Negative chronotropic action
78
SA node membrane potential (mV)
SA Node Action Potential
Voltage-gated Ca+2 channels
Voltage-gated K+ channels
0
-50
If or pacemaker channels
200 msec
79
CAUSES OF THE PACEMAKER
POTENTIAL
if
iCa
K+
iK
Na+
Ca++
OUT
IN
80
3) Ca2+ channel permeability decrease
 myocardial contractility decrease
 negative inotropic action
81
Role of Cardiac Ca2+
Channels
• Nodal cells
• initiate and propagate action
potentials- SLOW
• Non nodal cells
• controls action potential duration
• contraction
82
4) Ca2+ channel permeability decrease
depolarization rate of slow response cells decrease
conductivity of these cell decrease
 negative dromotropic action
83
SA node membrane potential (mV)
SA Node Action Potential
Voltage-gated Ca+2 channels
Voltage-gated K+ channels
0
No inward-rectifier
K+ channels
-50
If or pacemaker channels
200 msec
84
2. Effects of Sympathetic Nerve and catecholamine on
the Properties of Cardiac Muscle
Sympathetic nerve release norepinephrine from the
postganglionic endings;
epinephrine and norepinephrine released from the
adrenal glands
binding with β1 receptor on cardiac cells
 increase the Ca2+ channel permeability 
85
Ca2+ channel permeability increase:
Increase the spontaneous depolarization rate at phase 4
automaticity of SA node cell rise
heart rate increase
 Positive chronotropic action
86
Ca2+ channel permeability increase:
Increase the depolarization rate (slope) and amplitude at
phase 0
increase the conductivity of slow response cells
 Positive dromotropic action
Increase the Ca2+ concentration in plasma during excitation
myocardial contractility increase
 positive inotropic action
87
88
Effect of autonomic nerve activity on the heart
Region affected
Sympathetic Nerve
Parasympathetic Nerve
SA node
Increased rate of diastole Decreased rate of diastole
depolarization ; increased depolarization ; Decreased
cardiac rate
cardiac rate
AV node
Increase conduction rate Decreased conduction rate
Atrial muscle
Increase strength of
contraction
Decreased strength of
contraction
Ventricular
muscle
Increased strength of
contraction
No significant effect
89
IV The Normal Electrocardiogram (ECG)
Concept: The record of potential fluctuations of
myocardial fibers at the surface of the body
90
1 The Basic Mechanism
91
The Heart
is a pump
has electrical activity
(action potentials)
generates electrical
current that can be measured
on the skin surface (the ECG)
92
Currents and Voltages
At rest, Vm is
constant
No current flowing
Inside of cell is at
constant potential
Outside of cell is at
constant potential
A piece of cardiac muscle
inside
-----------------------------++++++++++++++++++
outside
-
+
0 mV
93
Currents and Voltages
A piece of cardiac muscle
 During AP upstroke,
Vm is NOT constant
 Current IS flowing
 Inside of cell is NOT
at constant potential
 Outside of cell is NOT
at constant potential
An action potential propagating
toward the positive ECG lead
produces a positive signal
AP
inside
++++-----------------------------++++++++++++++
outside
current
-
+
Some positive
potential
94
More Currents and
Voltages
During Repolarization
A piece of cardiac muscle
A piece of totally depolarized
cardiac muscle
inside
------------+++++++++++
inside
+++++++++++++++++++
+++++++------------------outside
------------------------------outside
Vm not changing
No current
No ECG signal
current
Repolarization spreading toward
the positive ECG lead produces
a negative response
Some negative potential
-
+
95
The ECG
 Can record a reflection of cardiac
electrical activity on the skin- EKG
 The magnitude and polarity of the signal
depends on
 what the heart is doing electrically
 depolarizing
 repolarizing
 whatever
 the position and orientation of the recording
96
electrodes
Cardiac Anatomy
Superior
vena cava
Pulmonary
veins
Sinoatrial (SA)A node
Atrial muscle
Atrioventricular (AV) node
Left atrium
Mitral valve
Internodal
conducting
tissue
Tricuspid valve
Ventricluar
muscle
Inferior
vena cava
Purkinje
fibers
Descending aorta
97
Flow of Cardiac
Electrical Activity
SA node
Internodal
conducting
fibers
Atrial muscle
Atrial muscle
AV node (slow)
Purkinje fiber
conducting system
Ventricular muscle
98
Conduction in the
Heart
0.12-0.2 s
approx. 0.44 s
Superior
vena cava
SA
node
Pulmonary
veins
SA node
Atrial muscle
Atria
AV
node
Ventricle
Left atrium
Mitral valve
Specialized
conducting
tissue
Tricuspid valve
Purkinje
AV node
Ventricluar
muscle
Inferior
vena cava
Purkinje
fibers
99
Descending aorta
2. The Normal ECG
Right Arm
“Lead II”
approx. 0.44 s
0.12-0.2 s
QT
PR
Left Leg
Atrial muscle
depolarization
R
T
P
Q
S
Ventricular muscle
depolarization
Ventricular
muscle
repolarization
100
Action Potentials in
the Heart
0.12-0.2 s
approx. 0.44 s
PR
QT
Superior
vena cava
ECG
Pulmonary artery
SA
Atria
AV
Pulmonary
veins
Ventricle
AV node
SA node
Left atrium
Atrial muscle
Mitral valve
Specialized
conducting
tissue
Tricuspid valve
Purkinje
Aortic artery
Ventricluar
muscle
Inferior
vena cava
Interventricular
septum
Purkinje
fibers
Descending aorta
101
102
Start of ECG Cycle
103
Early P Wave
104
Later in P Wave
105
Early QRS
106
Later in QRS
107
S-T Segment
108
Early T Wave
109
Later in T-Wave
110
Back to where we
started
111
3. Uses of the ECG
Heart Rate
Conduction in the heart
Cardiac arrhythmia
Direction of the cardiac vector
Damage to the heart muscle
Provides NO information about pumping
or mechanical events in the heart.
112