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ELECTRICAL PROPERTIES OF THE HEART
Sandor Gyorke, Ph.D.Office: DHLRI 507
Telephone: 292-3969Email: sandor.gyorke@osumc.edu
Learning Objectives• Differentiate pacemaker cells from myocardial cells by
action potential characteristics and ion transport during depolarization and repolarization and response to sympathetic and parasympathetic stimulation.
• Describe the sequence of activation of the heart and relate to the components of the electrocardiogram.
• Identify the components of the conduction system of the heart.
At the end of this module, you will learn to
Learning Resources
Pathophysiology of Heart Disease. Fifth Edition, Ed. L.S. Lilly, Lippincott Williams & Wilkins, Baltimore, MD, 2011 (pp. 12-23; 75-112)
D.E. Mohrman & L.J. Heller. Cardiovascular Physiology, 8th edition, McGraw-Hill, New York 2014.
Topics• Membrane excitability • Cardiac resting potential • Cardiac action potentials• Heart rhythm • The sequence of electrical activation of the heart• Cardiac electrocardiogram (ECG)
Electrical excitation
Contraction
• Cardiac myocytes are electrically excitable cellscapable of generating and conducting action potentials
• Disturbances in normal periodic electrical activity result in cardiac arrhythmia.
• All electrical phenomena in the heart rely on movement of ions across membranes
• The heart is composed of cardiac muscle cells, cardiomyocytes.
• There are two types of cardiac cells: “working” cardiomyocytes with fast action potential (in ventricles and atria) and cardiac pacemaker cells with slow action potential.
Introduction
Internal External[Na+] 15 mM 150 mM[K+] 150 mM 5 mM[Cl-] 5 mM 120 mM [Ca2+] 10-7 M 2 mM
Ca2+Na+
K+
Na+ Ca2+Ca2+
Na+
sarcolemmaChannels
Pumps
Sarcolemma:• Phospholipid bilayer• Pumps/transporters • Ion channels
K+
Transport and Distribution of Ions in Cardiac Myocytes
Background (IKr) Responsible for generation Kir2.1K+ current of the resting potential
Diastolic pacemaker (If) Responsible for spontaneous HCN2 current depolarization in pacemaker cells
Fast Depolarizing (INa) Initial depolarization SCN5A Na+ current of cardiac action potentials
Delayed repolarizing (IK) Helps to terminate action HERG K+ current potential plateau
Slow Ca2+ current (ICa) Important for plateau phase α 1C of action potential
Current Abbreviation Role Gene
Major Cardiac Voltage-gated Membrane Currents
PP
ATP ADP
Na+
K+
K+
Na+
2 K+
3 Na+ATPase
3 Na+
2 K+
• 3Na+/2K+• 150 cycles/sec• Maintenance of Na+ and K+
gradients requires ~20% of total ATP produced by the cell
in/out: 15/150 mM
in/out: 150/5 mM
inside
outside
Na - K ATPase (The Sodium-Potassium ATPase pump)
[K+]i
(150 mM) [K+]o
(5 mM)
K+
+ -+ -
+ -
K+
Na+
V
VM = -90 mV
Polarized state that makes possible generation of electrical signals
IKr
12
3
1) The Na/K-ATPase generates a K+ gradient by utilizing energy stored in ATP;
2) K+ flows out of the cell through K+ channels leaving behind anions; 3) K+ moves back attracted by the negative charge at the inner membrane face;
The Resting Membrane Potential
• Basis for signal-carrying ability of cardiac myocytes
• Allows large areas of the heart to contract almost simultaneously
• Drives cardiac rhythm
• Two main types: fast (non-pacemaker) and slow (pacemaker)
The Cardiac Action Potential
Mem
bran
e po
tent
ial
(m
V)
-100
0
+50
-100
0
+50
Nerve and skeletal muscle
Cardiac myocyte
• Can be recorded throughout most of the heart except the pacemaker and conduction regions
• The cardiac AP is much longer than the nerve and skeletal AP and is composed of a fast upstroke and a slow plateau
Upstroke Plateau
The Fast Action Potential
-100
0
+50Membrane potential (mV)
1 (Initial Repolarization)
2 (Plateau) 3
(Repolarization)
4 (Resting Potential)
4
gNa
gCa
gK
0 (Depolarization)
ION
CO
ND
UC
TAN
CE
S INa
ICa
IK IKrIKr
Phases of the Fast Action Potential
-100
0
+50Membrane potential (mV)
1 (Initial Repolarization)
2 (Plateau) 3
(Repolarization)
4 (Resting Potential)
4
gNa
gCa
gK
0 (Depolarization)
ION
CO
ND
UC
TAN
CE
S INa
ICa
IK IKrIKr
Phase 4 (Resting Potential )
Outside
Inside
K+
Outside
Inside
OutsideIKr IK
Inside
K+
Phases of the Fast Action Potential
-100
0
+50Membrane potential (mV)
1 (Initial Repolarization)
2 (Plateau) 3
(Repolarization)
4 (Resting Potential)
4
gNa
gCa
gK
0 (Depolarization)
ION
CO
ND
UC
TAN
CE
S INa
ICa
IK IKrIKr
Phase 0 (Depolarization )
Outside
Inside
Outside
Inside
OutsideIKr IK
Inside
Na+
Phases of the Fast Action Potential
-100
0
+50Membrane potential (mV)
1 (Initial Repolarization)
2 (Plateau) 3
(Repolarization)
4 (Resting Potential)
4
gNa
gCa
gK
0 (Depolarization)
ION
CO
ND
UC
TAN
CE
S INa
ICa
IK IKrIKr
Phase 0 (Depolarization )
Outside
Inside
Outside
Inside
OutsideIKr IK
Inside
Na+
Na+
Phases of the Fast Action Potential
-100
0
+50Membrane potential (mV)
1 (Initial Repolarization)
2 (Plateau) 3
(Repolarization)
4 (Resting Potential)
4
gNa
gCa
gK
0 (Depolarization)
ION
CO
ND
UC
TAN
CE
S INa
ICa
IK IKrIKr
Phase 1 (Initial Repolarization )
Outside
Inside
Outside
Inside
OutsideIKr IK
Inside
Phases of the Fast Action Potential
-100
0
+50Membrane potential (mV)
1 (Initial Repolarization)
2 (Plateau) 3
(Repolarization)
4 (Resting Potential)
4
gNa
gCa
gK
0 (Depolarization)
ION
CO
ND
UC
TAN
CE
S INa
ICa
IK IKrIKr
Phase 2 (Plateau)
Outside
Inside
K+
Outside
Inside
OutsideIKr IK
Inside
Ca2+
Phases of the Fast Action Potential
-100
0
+50Membrane potential (mV)
1 (Initial Repolarization)
2 (Plateau) 3
(Repolarization)
4 (Resting Potential)
4
gNa
gCa
gK
0 (Depolarization)
ION
CO
ND
UC
TAN
CE
S INa
ICa
IK IKrIKr
Phase 3 (Repolarization)
Outside
Inside
K+
Outside
Inside
OutsideIKr IK
InsideK+
Phases of the Fast Action Potential
Action Potential Contraction
Absoluterefractory period
Relative refractory period
Skeletal muscle fiber Cardiac myocyte
refractory period
• Inability to respond to further stimulation • Allows the ventricles sufficient time to empty their
content and refill before the next cardiac contraction
Refractory Periods
Me
mbr
an
e p
ote
ntia
l
(m
V)
-70
0
gNa
gCa
gK
ION
CO
ND
UC
TAN
CE
S If
ICa
IK
SA Node
AV Node
RepolarizationDepolarization
Pacemaker potential
4
0 3
4Threshold
The Pacemaker Action Potential
• Conducts both K+ and Na+
• Opens (inward current) at hyperpolarized potentials
• cAMP accelerates activation kinetics
• Responsible for initial phase of spontaneous depolarization in the nodal tissue
Properties of If
Vagal Symp
50Intrinsic Rate(60-100 bpm)
200 bpm
+ Norepinephrine+ Acetylcholine
Threshold
Positive chronotropic effect
Negativechronotropic effect
ACH NE
ACH
Vagal Symp
SA Node
Modulation of Pacemaker Activity
Gsb-R
b-Agonist
cAMPP
Ca2+ Channel
AC
ATP
ATP ADPCR
PKA
C
P
Na+/K+ Channel
Molecular Mechanisms of Positive Chronotropic Effects of β-AGONISTS
Gi
AchR
cAMP
Ca2+Channel
AC
ATP
Ach
P P
Na+/K+ Channel
Molecular Mechanisms of Negative Chronotropic Effects of Acetylcholine
• Electrical coupling of myocytes via gap junctions
• Cardiac conduction system
Conduction of Action Potentials Through the Heart
Gap junctions
Connexons
- - - - - - + + + + + + ++ + + + + + - - - - - -
• Large-conductance pores permeable for ions and small molecules
• Consist of two sets of six subunits (connexons)
• Responsible for electrical coupling of myocytes
Propagation of the Action Potential Along Cardiac Cells
Gap junctions
- - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + + - - - - - -
Connexons
• Large-conductance pores permeable for ions and small molecules
• Consist of two sets of six subunits (connexons)
• Responsible for electrical coupling of myocytes
Propagation of the Action Potential Along Cardiac Cells
SA Node
AV Node
Purkinjefibers
RV LV
LARA
Bundle of His
Left Bundle Branch
Right Bundle Branch
The Cardiac Conduction System
SA Node
AV Node
The Cardiac Conduction System
SA Node
AV Node
Conduction velocity ~0.5-1 m/sec Atrium activation occurs within ~100 ms nearly synchronously
The Cardiac Conduction System
AV Node Conduction velocity slows to ~0.2 m/sec This permits atrial relaxation occur before ventricularContraction begins
The Cardiac Conduction System
Bundle of His
Left Bundle Branch
Right Bundle Branch
Conduction velocity is fast ~4 m/sec so the entire ventricle is activated simultaneously
The Cardiac Conduction System
Purkinjefibers
Conduction velocity is fast ~4 m/sec so the entire ventricle is activated nearly simultaneously
The Cardiac Conduction System
The Electrocardiogram
ECG is a noninvasive recording of electrical activity of the working heart
A most commonly used diagnostic tool that provides information on:
• Anatomical orientation of the heart• Relative sizes of chambers• Disturbances of rhythm and conduction• Extent, location of ischemic damage
Represents the sum of action potentials occurring simultaneously in many individual cells
- - - - - - - - -+ + + + + + + + +
- - - - - - - - -+ + + + + + + + +
- - - - - - - - -+ + + + + + + + +
- - - - - - - - -+ + + + + + + + +
- - - - - - - - -+ + + + + + + + + - - - - - - - - -
+ + + + + + + + +
Depolarization- - - - - - - - -+ + + + + + + + +
- - - - - - - - -+ + + + + + + + +
(+) (-)
Extracellular Recording of Depolarization and Repolarization in a Strip of Cardiac Muscle
RA(-)
Polarity: When LL becomes positive with respect to RA an upward deflection is recorded
+ +
+
+- ---
+
-
LL (+)
ECG Recording as a Wave of Depolarization Along the Longitudinal Axis of Heart
P
Q
R
S
T
PR interval<0.2 s
QT interval~0.4 s
P w
ave
PR
se
gm
en
t
ST
se
gm
en
t
T w
ave
QR
S c
om
ple
x
Polarity: When LL becomes positive with respect to RA an upward deflection is recorded
P wave – atrial depolarization
QRS complex – ventricular depolarization
T wave – ventricular repolarization
PR interval – passage through the AV conduction system
QT interval – period of electrical systole
RA(-)
LL (+)
Components of a Typical ECG Recording
P
Q
R
S
T
PR interval<0.2 s
QT interval~0.4 s
P w
ave
PR
se
gm
en
t
ST
se
gm
en
t
T w
ave
QR
S c
om
ple
x
P wave – atrial depolarization
QRS complex – ventricular depolarization
T wave – ventricular repolarization
PR interval – passage through the AV conduction system
QT interval – period of electrical systole
RA(-)
LL (+)
Polarity: When LL becomes positive with respect to RA an upward deflection is recorded
Components of a Typical ECG Recording
SA Node
AV Node
P QRS T
+
_
The Sequence of Activation of Heart in Relation to ECG
SA Node
AV Node
P QRS T
Atrial depolarization
+
_
The Sequence of Activation of Heart in Relation to ECG
SA Node
AV Node
P QRS T
Depolarization of theintraventricular septum
+
_
The Sequence of Activation of Heart in Relation to ECG
SA Node
AV Node
P QRS T
Depolarization of large part of ventricular myocardium
+
_
The Sequence of Activation of Heart in Relation to ECG
SA Node
AV Node
P QRS T
Depolarization of a small portion of ventricular myocardiumnear the base
+
_
The Sequence of Activation of Heart in Relation to ECG
SA Node
AV Node
P QRS T
Depolarization of whole ventricular myocardium
+
_
The Sequence of Activation of Heart in Relation to ECG
SA Node
AV Node
P QRS T
Ventricular repolarization (progresses from the apex to the base)
+
_
The Sequence of Activation of Heart in Relation to ECG
Summary• For contraction to occur cardiac cells rely on action potentials (APs).
The rapid upstroke of APs of atrial and ventricular cells is due to a Na+ current (INa). The prolonged plateau phase of these APs is due to a Ca2+ current (ICa), repolarization to potassium currents (IK), and the resting potential is due to another potassium current called IK1.
• APs in pacemaker cells rely on ICa for their upstroke, IK to repolarize, and on a funny current (If) to provide the diastolic pacemaker potential which slowly depolarizes the membrane between APs.
• Normally APs are generated in the SA node. The impulse propagates from the SA node to both atria and to the AV node, where a delay occurs. The impulse then passes into the bundles of His, right and left bundle branches, Purkinje fibers, and working ventricular myocytes.
• The electrocardiogram (ECG) is recorded from the surface of the body and traces the conduction of the cardiac impulse through the heart.
Electrical Properties of the Heart Quiz
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Questions? sandor.gyorke@osumc.edu
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