Transcript section 2
LIU Chuan Yong
刘传勇
Institute of Physiology
Medical School of SDU
Tel 88381175 (lab)
88382098 (office)
Email: [email protected]
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
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
7
time
ELECTROPHYSIOLOGY OF THE
FAST VENTRICULAR MUSCLE
+20
AMP
1
2
0
0
3
Cardiac Cell
4
-90
0
300
t (msec)
8
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
9
Ion Channels in Working
Muscle
Essentially same in atrial and
ventricular muscle
Best understood in ventricular
cells
10
Ion Channels in Ventricular
Cells
Voltage-gated Na+ channels
Inward rectifier K+ channels
L-type Ca2+ channels
Several Voltage-gated K+ channels
11
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
12
+20
1
2
0
0
3
4
-90
0
300
t (msec)
13
Inward Rectifier (Ik1)
Structure
Note: No “voltage sensor”
P-Region
Extracellular
Fluid
M1
M2
membrane
Inside
H2N
HO2C
14
Inward Rectifier
Channels
Current
0
Ek
-120
-100
-80
-60
-40
-20
Vm (mV)
0
20
40
60
15
Inward Rectification
K+
K+
Mg2+
Mg2+
K+
K+
K+
K+
-80
-30 mV
mV
K+
16
Intracellular Solution
Extracellular solution
K+
K+
Inward Rectifier
Channels
Current
0
Ek
-120
-100
-80
-60
-40
-20
Vm (mV)
0
20
40
60
17
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
18
+20
1
2
0
0
3
4
-90
0
300
t (msec)
19
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
20
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
21
Role of Cardiac Ca2+
Channels
Nodal cells
initiate and propagate action
potentials- SLOW
Non nodal cells
controls action potential duration
contraction
22
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
23
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
24
OVERVIEW OF SPECIFIC EVENTS
IN THE VENTRICULAR ACTION
POTENTIAL
25
Activation & Fast Inactivation
26
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
27
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
28
Ion Channels in Ventricular
Muscle
Current
Na Current
Ca Current
IK1
ITO
IKur
IKr
IKs
29
2. Transmembrane
Potential of Rhythmic
Cells
30
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
31
Activated by negative potential (at about -60 mv
during Phase 3)
32
+
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.
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
33
B, Sinoatrial node cell
SA node membrane potential (mV)
SA Node Action Potential
Voltage-gated Ca channels
0
Voltage-gated K channels
No inward-rectifier
K channels
-50
If or pacemaker channels
200 msec
34
SA Node Cells
Current
Ca Current
K currents
If
(pacemaker current)
35
CAUSES OF THE PACEMAKER
POTENTIAL
if
iCa
K+
iK
Na+
Ca++
OUT
IN
36
LOOKING AT THE
PACEMAKER CURRENTS
voltage
iK
if
ionic currents
iCa
37
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
38
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
39
II Electrical Properties of
Cardiac Cells
Excitability, Conductivity and
Automaticity
40
1. Excitability of Cardiac Muscle
41
(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
42
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
43
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
44
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.
45
Refractory Period
Long refractory
period prevents
tetanic contractions
systole and diastole
occur alternately.
very important for
pumping blood to
arteries.
46
Comparison of refractory period and summation
in cardiac and skeletal muscle fibers
47
Supranormal period:
Occurs early in phase 4 and is
usually accompanied by negative
after-potentials as some potassium
channels close.
The membrane potential is about 80 mv - -90 mv, near threshold
potential
Absolute
S.N.
Rel
48
49
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
50
2)
Premature excitation,
premature contraction
and compensatory pause
51
Extra-stimulus
premature
excitation
premature
contraction
compensatory
pause
52
2. Automaticity (Autorhythmicity)
53
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 pacemaker
latent pacemaker
ectopic pacemaker
54
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
55
(3) Factors determining automaticity
Depolarization rate
of phase 4
Threshold
potential
The maximal
repolarization
potential
56
3. Conductivity
57
(1) Pathways and characteristics
of conduction in heart
58
Conducting System of Heart
59
THE CONDUCTION SYSTEM OF THE HEART
60
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
61
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
62
(2) Factors determining conductivity
Anatomical factors
Physiological factors
63
Anatomical factors
Gap junction between working cells
functional atrial and ventricular syncytium
64
65
Multi-cellular
Organization
= Gap Junction Channel
66
Anatomical factors
Gap junction between working cells
and functional atrial and ventricular
syncytium
Diameter of the cardiac cell –
conductive resistance – conductivity
67
Physiological factors
A. Slope of depolarization and amplitude of
phase 0
Fast and slow response cells
B. Excitability of the adjacent unexcited
membrane
68
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 Ca2+ channel permeability decrease
69
ACh on Atrial Action
Potential
( ) K+ Conductance
(Efflux)
0 mv
- 90mv
Time
70
1) K+ channel permeability increase
resting potential (maximal diastole potential)
more negative
excitability decrease
71
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
72
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
73
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
74
CAUSES OF THE PACEMAKER
POTENTIAL
if
iCa
K+
iK
Na+
Ca++
OUT
IN
75
3) Ca2+ channel permeability decrease
myocardial contractility decrease
negative inotropic action
76
Role of Cardiac Ca2+
Channels
• Nodal cells
• initiate and propagate action
potentials- SLOW
• Non nodal cells
• controls action potential duration
• contraction
77
4) Ca2+ channel permeability decrease
depolarization rate of slow response cells decrease
conductivity of these cell decrease
negative dromotropic action
78
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
79
2. Effects of Sympathetic Nerve and catecholamine
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
80
Ca2+ channel permeability increase:
Increase the spontaneous depolarization rate at phase 4
automaticity of SA node cell rise
heart rate increase
Positive chronotropic action
81
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
82
83
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
84
IV The Normal Electrocardiogram (ECG)
Concept: The record of potential fluctuations of
myocardial fibers at the surface of the body
85
1 The Basic Mechanism
86
The Heart
is a pump
has electrical activity
(action potentials)
generates electrical
current that can be measured
on the skin surface (the ECG)
87
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
88
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
89
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
-
+
90
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
91
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
92
Flow of Cardiac
Electrical Activity
SA node
Internodal
conducting
fibers
Atrial muscle
Atrial muscle
AV node (slow)
Purkinje fiber
conducting system
Ventricular muscle
93
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
94
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
95
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
96
97
Start of ECG Cycle
98
Early P Wave
99
Later in P Wave
100
Early QRS
101
Later in QRS
102
S-T Segment
103
Early T Wave
104
Later in T-Wave
105
Back to where we
started
106
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.
107