LIU Chuan Yong 刘传勇 Institute of Physiology Medical School of SDU Tel 88381175 (lab)

1

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

mailto:[email protected]

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Section 2

Electrophysiology of the Heart

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CARDIAC CARDIAC ELECTROPHYSIOLOGYELECTROPHYSIOLOGY

4

1, The working cells.

Special property: contractility

Two kinds of cardiac cells

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including the

Sinoatrial node, Atrioventricular node,

Atrioventricular bundle (bundle of His),

and Purkinje system.

Special property: automaticity

2, Special conduction system

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I. Transmembrane Potentials of

Myocardial Cells

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ACTION POTENTIALS FROM DIFFERENT AREAS OF THE HEARTFast and Slow Response

mv

0

-90mv

mv

0

-90mv

mv0

-80mv

ATRIUM VENTRICLE

SA NODE

time

8

ELECTROPHYSIOLOGY OF THE FAST VENTRICULAR MUSCLE

mv

t (msec)

-90

0

+20

0 300

0

12

3

4

Cardiac Cell

AMP

To oscillosco

pe

9

mv

t (msec)

-90

0

+20

0 300

0

12

3

4

Phase 0: rapid depolarization, 1-2ms

Phase 1: early rapid repoarization, 10 ms

Phase 2: plateau, slow repolarization, the potential is around 0 mv. 100 – 150ms

Phase 3, late rapid repolarization. 100 – 150 ms

Phase 4 resting potentials

General description

Resting potential: -90mv

Action Potential

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Ion Channels in Working Muscle Essentially same in atrial and vent

ricular muscle Best understood in ventricular cel

ls

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Ion Channels in Ventricular Cells

Voltage-gated Na+ channels Inward rectifier K+ channels L-type Ca2+ channels Several Voltage-gated K+ channels

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Cardiac Na+ Channels Almost identical to nerve Na+ channels (st

ructurally 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

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mv

t (msec)

-90

0

+20

0 300

0

12

3

4

14

Inward Rectifier (Ik1) Structure

M1 M2

HO2CH2N

Inside

P-Region

ExtracellularFluid

membrane

Note: No “voltage sensor”

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Inward Rectifier Channels

-120 -100 -80 -60 -40 -20 0 20 40 60

Cur

rent

Vm (mV)

0

Ek

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Inward RectificationEx

trace

llula

r sol

utio

n

Intra

cellu

lar S

olut

ion

-80 mV-30 mV

K+

K+

Mg2+

K+

K+

K+

K+

K+

Mg2+

K+

K+

17

Inward Rectifier Channels

-120 -100 -80 -60 -40 -20 0 20 40 60

Cur

rent

Vm (mV)

0

Ek

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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

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mv

t (msec)

-90

0

+20

0 300

0

12

3

4

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Cardiac Voltage-gated 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

Inactivating K channels (ITO)

“Rapid” K channels (IKr)

“Slow” K channels (IKs)

“Ultra-rapid” K channels (IKur)

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Cardiac Ca2+ 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

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Role of Cardiac Ca2+ Channels Nodal cells

initiate and propagate action potentials- SLOW

Non nodal cells controls action potential duration contraction

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Ca2+CHANNEL BLOCKERS AND THE CARDIAC CELL ACTION POTENTIAL

DILTIAZEM 地尔硫卓 10 µMol/L30 µMol/L10

30

10

FOR

CE

AC

TIO

N P

OT

EN

TIA

L

TIME

CONTROL

CONTROL

30

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Ion Channels in Atrial Cells

Same as for ventricular cells Less pronounced plateau due to different

balance of voltage-gated Ca2+ and K channels

mv

0

-90mv

mv

0

-90mv

ATRIUM VENTRICLE

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OVERVIEW OF SPECIFIC EVENTS IN THE VENTRICULAR ACTION

POTENTIAL

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Activation & Fast Inactivation

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PHASE 0 OF THE FAST FIBER ACTION POTENTIAL

hm

Na+

-90mvA

Na+

mmh-65mv

B

mh

Na+

0mvC m

h

Na+

D+20mv

Na+

mh+30mv

E

ChemicalGradient

ElectricalGradient

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Ion Channels in Ventricular Muscle

Ven

tricu

lar m

uscl

e m

embr

ane

pote

ntia

l (m

V)

-50

0

200 msec




IK1

Voltage-gated Na Channels


Voltage-gatedCa Channels

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Current

Na Current

Ca Current

IK1

ITO

IKur

IKs

IKr

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2. Transmembrane Potential of Rhythmic Cells

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Ion Channels in Ion Channels in Purkinje FibersPurkinje 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

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Activated by negative potential (at about -60 mv during Phase 3)

Not particularly selective: allows both Na+ and K+

33A, Cardiac ventricular cell

B, Sinoatrial node cell

The SA node cell Maximal repolarization (d

iastole) potential, –70mv Low amplitude and long

duration of phase 0. not so sharp as ventricle cel

l and Purkinje cell. No phase 1 and 2 Comparatively fast sponta

neous depolarization at phase 4

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SA Node Action PotentialSA

nod

e m

embr

ane

pote

ntia

l (m

V)

0

-50

200 msecIf or pacemaker channels

Voltage-gated Ca channels

Voltage-gated K channels

No inward-rectifier K channels

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SA Node Cells

Ca Current

K currents

Current

If (pacemaker current)

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CAUSES OF THE PACEMAKER POTENTIAL

OUT

IN

Na+

if

Ca++

iCaK+

iK

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LOOKING AT THE PACEMAKER CURRENTS

voltage

ionic currentsiCa

iK

if

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AV Node Action PotentialsAV Node Action Potentials

Similar to SA node Latent pacemaker Slow, Ca+2-dependent

upstroke Slow conduction (delay) K+-dependent

repolarization

AV

nod

e m

embr

ane

pote

ntia

l (m

V)

0

-50

200 msecAV node

SA node

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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

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II Electrical Properties of Cardiac Cells

Excitability, Conductivity and Automaticity

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1. Excitability of Cardiac Muscle

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+25

Time (msec)0 0.1 0.2 0.3-125

-100-75-50

-250

0

4

1

2 3

Tra

nsm

embr

ane

Pote

ntia

l RRP

ARP

Absolute Refractory Period – regardless of the strength of a stimulus, the cell cannot be depolarized.

Relative Refractory Period – stronger than normal stimulus can induce depolarization.

(1) Refractory Period(1) Refractory Period

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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

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Na+ Channel Conformations

Conductingconformation

Non-conductingconformation(s)

(at negative potentials) (shortly after more depolarized potentials)

Another Non-conductingconformation

(a while after moredepolarized potentials)

IFM IFM

IFM

Closed Open InactivatedOutside

Inside

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Refractory Period The plateau phase of the ca

rdiac 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 ne

urons and skeletal muscle fibers.

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Refractory Period Long refractory period

prevents tetanic contractions

systole and diastole occur alternately.

very important for pumping blood to arteries.

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Comparison of refractory period and summation in cardiac and skeletal muscle fibers

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Supranormal period: Occurs early in phase 4 and is usu

ally 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

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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

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2) Premature excitation, premature contraction and compensatory pause

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Extra-stimuluspremature excitation premature contraction compensatory pause

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2. Automaticity (Autorhythmicity)

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Automaticity (Autorhythmicity) Some tissues or cells have the ability to pro

duce 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

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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

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(3) Factors determining automaticity Depolarization rate

of phase 4 Threshold potential The maximal repol

arization potential

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3. Conductivity

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(1) Pathways and characteristics of conduction in heart

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Conducting System of Heart

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THE CONDUCTION SYSTEM OF THE HEART

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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

VentricularMuscle

1m/s

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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

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(2) Factors determining conductivity

Anatomical factors

Physiological factors

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Anatomical factors Gap junction between working cells

functional atrial and ventricular syncytium

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Multi-cellular Organization

= Gap Junction Channel

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Anatomical factors

Gap junction between working cells and functional atrial and ventricular syncytium

Diameter of the cardiac cell – conductive resistance – conductivity

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Physiological factorsA. Slope of depolarization and amplitude of

phase 0 Fast and slow response cells

B. Excitability of the adjacent unexcited membrane

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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

70Time

Volta

ge

- 90mv

0 mv ( ) K+ Conductance (Efflux)

ACh on Atrial Action Potential

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1) K+ channel permeability increase resting potential (maximal diastole potential) more negative excitability decrease

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Ven

tricu

lar m

uscl

e m

embr

ane

pote

ntia

l (m

V)

-50

0

200 msec




IK1

Voltage-gated Na Channels


Voltage-gatedCa Channels

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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

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nod

e m

embr

ane

pote

ntia

l (m

V)

0

-50


Voltage-gated Ca+2 channels

Voltage-gated K+ channels

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CAUSES OF THE PACEMAKER POTENTIAL

OUT

IN

Na+

if

Ca++

iCa K+

iK

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3) Ca2+ channel permeability decrease

myocardial contractility decrease

negative inotropic action

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Role of Cardiac Ca2+ Channels• Nodal cells

• initiate and propagate action potentials- SLOW

• Non nodal cells• controls action potential duration• contraction

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4) Ca2+ channel permeability decrease

depolarization rate of slow response cells decrease

conductivity of these cell decrease

negative dromotropic action

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nod

e m

embr

ane

pote

ntia

l (m

V)

0

-50


Voltage-gated Ca+2 channels

Voltage-gated K+ channels

No inward-rectifier K+ channels

80

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

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Increase the spontaneous depolarization rate at phase 4

automaticity of SA node cell rise

heart rate increase

Positive chronotropic action

Ca2+ channel permeability increase:

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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

Ca2+ channel permeability increase:

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Effect of autonomic nerve activity on the heart

Region affected Sympathetic Nerve Parasympathetic Nerve

SA node Increased rate of diastole depolarization ; increased cardiac rate

Decreased rate of diastole depolarization ; Decreased 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

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IV The Normal Electrocardiogram (ECG)

Concept: The record of potential fluctuations of myocardial fibers at the surface of the body

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1 The Basic Mechanism

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The Heartis a pump

has electrical activity(action potentials)

generates electricalcurrent that can be measured on the skin surface (the ECG)

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Currents and VoltagesAt rest, Vm is const

antNo current flowingInside of cell is at c

onstant potentialOutside of cell is at

constant potential

++++++++++++++++++

------------------------------

A piece of cardiac muscle

outside

inside

0 mV

+-

89

Currents and Voltages During AP upstroke,

Vm is NOT constant Current IS flowing Inside of cell is NOT a

t constant potential Outside of cell is NOT

at constant potential

++++------------------------------++++++++++++++


outside

inside

Some positive potential+-

current

AP

An action potential propagatingtoward the positive ECG lead produces a positive signal

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More Currents and Voltages

current

-------------------------------

A piece of totally depolarizedcardiac muscle

outside

inside+++++++++++++++++++

Vm not changingNo currentNo ECG signal

+++++++-------------------


outside

inside------------+++++++++++

During Repolarization

+-Some negative potential

Repolarization spreading towardthe positive ECG lead producesa negative response

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The ECG Can record a reflection of cardiac electrical activit

y 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 electrodes

92

Cardiac Anatomy

Atrial muscleSinoatrial (SA)A node Left atrium

Descending aortaInferiorvena cava

Ventricluar

Pulmonaryveins

Superiorvena cava

Tricuspid valve

Mitral valve

Atrioventricular (AV) node

Purkinjefibers

muscle

Internodalconducting

tissue

93

Flow of Cardiac Electrical Activity

SA node Atrial muscle

AV node (slow)

Purkinje fiberconducting system Ventricular muscle

Internodalconductingfibers

Atrial muscle

94

Conduction in the Heart0.12-0.2 s approx. 0.44 s

SA

AtriaAtrial muscleSA node Left atrium


Ventricluar

Pulmonaryveins

Superiorvena cava

Tricuspid valve

Mitral valve

AV node

Purkinjefibers

muscle

Specializedconducting

tissue

Purkinje

Ventricle

node

nodeAV

95

2. The Normal ECG

P

Q

R

S

T

Right Arm

Left Leg

QTPR

0.12-0.2 s approx. 0.44 s

Atrial muscledepolarization

Ventricular muscledepolarization

Ventricular musclerepolarization

“Lead II”

96

Action Potentials in the Heart

AV

Purkinje

Ventricle

Aortic artery

Left atrium


Ventricluar

Atrial muscle

Pulmonaryveins

Superiorvena cava

Pulmonary artery

Tricuspid valve

Mitral valve

Interventricularseptum

AV nodeSA node

ECGQTPR

0.12-0.2 s approx. 0.44 s

SA

Atria

Purkinjefibers

muscle

Specializedconducting

tissue

97

98

Start of ECG Cycle

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Early P Wave

100

Later in P Wave

101

Early QRS

102

Later in QRS

103

S-T Segment

104

Early T Wave

105

Later in T-Wave

106

Back to where we started

107

3. Uses of the ECGHeart RateConduction in the heartCardiac arrhythmiaDirection of the cardiac vectorDamage to the heart muscle

Provides NO information about pumping or mechanical events in the heart.

Documents

LIU Chuan Yong 刘传勇 Institute of Physiology Medical School of SDU Tel 88381175 (lab)