1. ELECTRICAL PROPERTIES OF THE HEART
Sandor Gyorke, Ph.D.
Office: DHLRI 507
Telephone:
ELECTRICAL PROPERTIES OF THE HEART

2. At the end of this module, you will learn to
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.

3. Learning Resources
Pathophysiology of Heart Disease. Fifth Edition, Ed. L.S. Lilly, Lippincott Williams & Wilkins, Baltimore, MD, 2011 (pp ; ) D.E. Mohrman & L.J. Heller. Cardiovascular Physiology, 8th edition, McGraw-Hill, New York 2014.

4. Topics Membrane excitability Cardiac resting potential
Cardiac action potentials
Heart rhythm
The sequence of electrical activation of the heart
Cardiac electrocardiogram (ECG)

5. Introduction
The heart is composed of cardiac muscle cells, cardiomyocytes.
Cardiac myocytes are electrically excitable cells
capable of generating and conducting action potentials
Electrical
excitation
Contraction
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.
All electrical phenomena in the heart rely on movement of ions across membranes
Disturbances in normal periodic electrical activity result in cardiac arrhythmia.

6. Transport and Distribution of Ions in Cardiac Myocytes
Na+
Ca2+
Channels
sarcolemma K+
Na+
Ca2+
Ca2+
Pumps
Na+ K+
Internal External
[Na+] mM mM
[K+] mM mM
[Cl-] mM mM
[Ca2+] M mM
Sarcolemma:
Phospholipid bilayer
Pumps/transporters
Ion channels

7. Major Cardiac Voltage-gated Membrane Currents
Current Abbreviation Role Gene
Fast Depolarizing (INa) Initial depolarization SCN5A
Na+ current of cardiac action potentials
Slow Ca2+ current (ICa) Important for plateau phase α 1C
of action potential
Delayed repolarizing (IK) Helps to terminate action HERG
K+ current potential plateau
Background (IKr) Responsible for generation Kir2.1
K+ current of the resting potential
Diastolic pacemaker (If) Responsible for spontaneous HCN2
current depolarization in pacemaker
cells

8. Na - K ATPase (The Sodium- Potassium ATPase pump)
ADP
outside
3 Na+
inside P P
2 K+
in/out: 15/150 mM
Na+
3Na+/2K+
150 cycles/sec
Maintenance of Na+ and K+ gradients requires ~20% of total ATP produced by the cell
Na+
3 Na+
ATPase K+
2 K+ K+
in/out: 150/5 mM

9. The Resting Membrane Potential
Polarized state that makes possible generation of electrical signals 1 2
[K+]i
(150 mM)
VM = -90 mV
[K+]o
(5 mM) V
IKr K+ K+
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;
+ -
Na+
+ - 3
+ -

10. The Cardiac Action 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)

11. The Fast Action Potential
Nerve and skeletal
muscle
+50
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
Membrane potential (mV)
-100
Cardiac myocyte
+50
-100
Upstroke
Plateau

12. Phases of the Fast Action Potential
+50
1 (Initial Repolarization)
Membrane
potential
(mV) 2
(Plateau)
(Depolarization) 3
(Repolarization) 4 4
(Resting Potential)
-100
gNa
INa
ICa
ION CONDUCTANCES
gCa gK
IKr IK
IKr

13. Phases of the Fast Action Potential
+50
1 (Initial Repolarization)
Membrane
potential
(mV)
Phase 4 2
(Plateau)
(Resting Potential )
(Depolarization) 3
(Repolarization) 4 4
(Resting Potential)
-100
gNa
Outside
INa
Inside
Outside
ICa
ION CONDUCTANCES
gCa
Inside
IKr K+ IK gK
Outside
Inside
IKr IK
IKr K+

14. Phases of the Fast Action Potential
+50
1 (Initial Repolarization)
Membrane
potential
(mV)
Phase 0 2
(Plateau)
(Depolarization )
(Depolarization) 3
(Repolarization) 4 4
(Resting Potential)
-100
Na+
gNa
Outside
INa
Inside
Outside
ICa
ION CONDUCTANCES
gCa
Inside
IKr IK gK
Outside
Inside
IKr IK
IKr

15. Phases of the Fast Action Potential
+50
1 (Initial Repolarization)
Membrane
potential
(mV)
Phase 0 2
(Plateau)
(Depolarization )
(Depolarization) 3
(Repolarization) 4 4
(Resting Potential)
-100
Na+
gNa
Outside
INa
Inside
Na+
Outside
ICa
ION CONDUCTANCES
gCa
Inside
IKr IK gK
Outside
Inside
IKr IK
IKr

16. Phases of the Fast Action Potential
+50
1 (Initial Repolarization)
Membrane
potential
(mV)
Phase 1 2
(Plateau)
(Initial Repolarization )
(Depolarization) 3
(Repolarization) 4 4
(Resting Potential)
-100
gNa
Outside
INa
Inside
Outside
ICa
ION CONDUCTANCES
gCa
Inside
IKr IK gK
Outside
Inside
IKr IK
IKr

17. Phases of the Fast Action Potential
+50
1 (Initial Repolarization)
Membrane
potential
(mV)
Phase 2 2
(Plateau)
(Plateau)
(Depolarization) 3
(Repolarization) 4 4
(Resting Potential)
-100
gNa
Outside
INa
Inside
Ca2+
Outside
ICa
ION CONDUCTANCES
gCa
Inside
IKr IK gK
Outside
Inside
IKr IK
IKr K+

18. Phases of the Fast Action Potential
+50
1 (Initial Repolarization)
Membrane
potential
(mV)
Phase 3 2
(Plateau)
(Repolarization)
(Depolarization) 3
(Repolarization) 4 4
(Resting Potential)
-100
gNa
Outside
INa
Inside
Outside
ICa
ION CONDUCTANCES
gCa
Inside
IKr IK gK
Outside
Inside IK
IKr
IKr K+ K+

19. Refractory Periods Skeletal muscle fiber Cardiac myocyte Contraction
Action Potential
Relative
refractory
period
refractory period
Absolute
refractory period
Inability to respond to further stimulation
Allows the ventricles sufficient time to empty their content and refill before the next cardiac contraction

20. The Pacemaker Action Potential
Repolarization
SA Node
Depolarization
Membrane potential
(mV)
AV Node 3
Threshold 4 4
-70
Pacemaker potential If
gNa
ICa
gCa
ION CONDUCTANCES gK IK

21. Properties of If 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

22. Modulation of Pacemaker Activity
Vagal
Symp
Vagal
Symp
ACH
Intrinsic
Rate
( bpm) 50
200 bpm
ACH NE
SA Node
+ Norepinephrine
+ Acetylcholine
Threshold
Positive
chronotropic
effect
Negative
chronotropic
effect

23. Molecular Mechanisms of Positive Chronotropic Effects of β-AGONISTS
Ca2+
Channel
Na+/K+
Channel b
-Agonist AC b -R Gs P P
ATP
cAMP C
ADP R C
ATP
PKA

24. Molecular Mechanisms of Negative Chronotropic Effects of Acetylcholine
Ca2+
Channel
Na+/K+
Channel
Ach AC
AchR Gi
ATP
cAMP P P

25. Conduction of Action Potentials Through the Heart
Electrical coupling of myocytes via gap junctions
Cardiac conduction system

26. Propagation of the Action Potential Along Cardiac Cells
Connexons
Large-conductance pores permeable for ions and small molecules
Consist of two sets of six subunits (connexons)
Responsible for electrical coupling of myocytes
Gap junctions

27. Propagation of the Action Potential Along Cardiac Cells
Connexons
Large-conductance pores permeable for ions and small molecules
Consist of two sets of six subunits (connexons)
Responsible for electrical coupling of myocytes
Gap junctions

28. The Cardiac Conduction System
AV Node
Bundle of His
SA Node LA RA
Left Bundle Branch
Right Bundle
Branch LV RV
Purkinje
fibers

29. The Cardiac Conduction System
AV Node
SA Node

30. The Cardiac Conduction System
AV Node
Conduction velocity ~0.5-1 m/sec
Atrium activation occurs within ~100 ms nearly synchronously
SA Node

31. The Cardiac Conduction System
AV Node
Conduction velocity slows to ~0.2 m/sec
This permits atrial relaxation occur before ventricular
Contraction begins

32. 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

33. The Cardiac Conduction System
Conduction velocity is fast ~4 m/sec
so the entire ventricle is activated nearly simultaneously
Purkinje
fibers

34. 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

35. Extracellular Recording of Depolarization and Repolarization in a Strip of Cardiac Muscle
(+)
(-)

36. ECG Recording as a Wave of Depolarization Along the Longitudinal Axis of Heart- - - + RA
(-) - - + +
LL (+) + +
Polarity: When LL becomes
positive with respect
to RA an upward
deflection is recorded

37. Components of a Typical ECG Recording
QRS complex
PR segment
ST segment
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
P wave
T wave RA
(-) R
LL (+) T P
Polarity: When LL becomes
positive with respect
to RA an upward
deflection is recorded Q S PR
interval
<0.2 s
QT interval
~0.4 s

38. Components of a Typical ECG Recording
QRS complex
PR segment
ST segment
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
P wave
T wave RA
(-) R
LL (+) T P
Polarity: When LL becomes
positive with respect
to RA an upward
deflection is recorded Q S PR
interval
<0.2 s
QT interval
~0.4 s

39. The Sequence of Activation of Heart in Relation to ECG_
AV Node
SA Node P
QRS T +

40. The Sequence of Activation of Heart in Relation to ECG_
AV Node
SA Node P
QRS T
Atrial depolarization +

41. The Sequence of Activation of Heart in Relation to ECG_
AV Node
SA Node P
QRS T
Depolarization of the
intraventricular septum +

42. The Sequence of Activation of Heart in Relation to ECG_
AV Node
SA Node P
QRS T
Depolarization of large part of ventricular myocardium +

43. The Sequence of Activation of Heart in Relation to ECG_
AV Node
SA Node P
QRS T
Depolarization of a small portion of ventricular myocardium
near the base +

44. The Sequence of Activation of Heart in Relation to ECG_
AV Node
SA Node P
QRS T
Depolarization of whole ventricular myocardium +

45. The Sequence of Activation of Heart in Relation to ECG_
AV Node
SA Node P
QRS T
Ventricular repolarization (progresses from the apex to the base) +

46. 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.

47. Electrical Properties of the Heart Quiz

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