1. Cardiac Electrophysiology
Qiang XIA (夏强), PhD
Department of Physiology
School of Medicine
Tel: ,

2. The major types of cardiac muscle: Atrial muscle Ventricular muscle
Specialized excitatory and conductive muscle
Contractile cells
（收缩细胞）
Autorhythmic cells
（自律细胞）

3. Conducting system of the heart

4. Cardiac muscle

5. Sequence of cardiac excitation
The sinoatrial node is
the heart’s pacemaker
because it initiates
each wave of excitation
with atrial contraction.
The Bundle of His and other parts
of the conducting system deliver
the excitation to the apex of the
heart so that ventricular contraction
occurs in an upward sweep.

6. General process of excitation and contraction of cardiac muscle
Initiation of action potentials in sinoatrial node
Conduction of action potentials along specialized conductive system
Excitation-contraction coupling
Muscle contraction

7. Transmembrane potentials recorded in different heart regions

8. Transmembrane potential of ventricular cells and its ionic mechanisms
Resting Potential: -90 mV
Action Potential
Phase 0: Depolarization
Phase 1: Early phase of rapid repolarization
Phase 2: Plateau（平台期）
Phase 3: Late phase of rapid repolarization
Phase 4: Resting phase

9. Ionic mechanisms Resting potential K+ equilibrium potential
Na+-inward background current
Electrogenic Na+-K+ pump

10. The action potential of a
myocardial pumping cell.
Phase 0
Threshold potential (-70mV)
Opening of fast Na+ channel
Regenerative cycle（再生性循环）

11. Phase 1
Transient outward current, Ito
K+ current
activated at –20 mV
opening for 5~10 ms

12. Phase 2
Inward current Outward current
(Ca2+ & Na+) (K+ current)

13. Types of Ca2+ channels in cardiac cells:
(1) L-type (long-lasting) (Nowycky, 1985)
(2) T-type (transient) (Nowycky, 1985)

14. Ca2+ channels L-type T-type Duration of current long-lasting transient
Activation kinetics slower faster
Inactivation kinetics slower faster
Threshold high (-35mV) Low (-60mV)
cAMP/cGMP-regulated Yes No
Phosphorylation-regulated Yes No
Openers Bay-K
Blockers varapamil Tetramethrin
nifedipine, diltiazem Ni2+
Inactivation by [Ca2+]i Yes slight
Patch-clamp recording run-down relatively stable

15. Outward current (K+ current):
(1) inward rectifier K+ current (IK1)
(2) delayed rectifier K+ current (IK)

16. Inactivation of Ca2+ channel
Phase 3
Inactivation of Ca2+ channel
Outward K+ current dominates
IK: Progressively increased
IK1: Regenerative K+ Outward Current

17. Phase 4
Na+-Ca2+ exchange
Sarcolemmal Ca2+ pump
SR Ca2+ pump
Na+-K+ pump

19. a, The key ion channels (and an electrogenic transporter) in cardiac cells. K+ channels (green) mediate K+ efflux from the cell; Na+ channels (purple) and Ca2+ channels (yellow) mediate Na+ and Ca2+ influx, respectively. The Na+/Ca2+ exchanger (red) is electrogenic, as it transports three Na+ ions for each Ca2+ ion across the surface membrane.
b, Ionic currents and genes underlying the cardiac action potential. Top, depolarizing currents as functions of time, and their corresponding genes; centre, a ventricular action potential; bottom, repolarizing currents and their corresponding genes.
From the following article:
Cardiac channelopathies
Eduardo Marbán
Nature 415, (10 January 2002)
doi: /415213a

20. Transmembrane potentials recorded in different heart regions

21. Transmembrane potential of autorhythmic cells and its ionic mechanisms

22. Purkinje cells: Fast response autorhythmic cells4

23. Contractile cells Autorhythmic cells
Phase 4 stable potential Phase 4 spontaneous depolarization
（4期自动去极化）
Resting potential Maximal repolarization potential
（最大复极电位）

24. Phase 0~3：similar to ventricular cells Phase 4：
Ionic mechanism
Phase 0~3：similar to ventricular cells
Phase 4：
(1) If – Funny current, Pacemaker current（起搏电流）
(2) Ik Decay（钾电流衰减）

26. Characteristics of If channel
Na+, K+
Voltage- & time-dependent
Activation── Repolarized to -60mV
Full activation── Hyperpolarized to -100mV
Inactivation── Depolarized to -50mV
Blocked by Cs, not by TTX

27. Sinoatrial cells

28. Sinoatrial cells: Slow response autorhythmic cells4 3
Maximal repolarization potential -70mV
Threshold potential -40mV
Phase 0, 3, 4

29. Ionic mechanism
Phase 0: ICa (ICa,L) 4 3

30. Inactivation of L-type Ca2+ channel
Phase 3:
Inactivation of L-type Ca2+ channel
Outward K+ current (Ik) 4 3

31. Phase 4： Ik decay Inactivated when repolarized to -60mV ICa,T
Activated when depolarized to -50mV If

32. The action potential of an autorhythmic cardiac cell.

33. Electrocardiogram (ECG)（心电图）
The electrocardiogram (ECG) measures changes in skin electrical voltage/potential caused by electrical currents generated by the heart

34. Electrocardiogram (ECG)
The relationship between the electrocardiogram (ECG), recorded as the difference between currents at the left and right wrists,
and
an action potential typical of ventricular myocardial cells.
Electrocardiogram (ECG)

35. The standard 12 lead ECG Einthoven’s Triangle I II III aVR aVL aVF
Limb leads (Bipolar) (I, II, III)
Augmented limb leads (Unipolar) (aVR, aVL, aVF)
Chest leads (Unipolar) (V1, V2, V3, V4, V5, V6) I II
III
aVR
aVL
aVF
V1 V2 V3 V4 V5 V6
Willem Einthoven: Dutch physiologist. He won a 1924 Nobel Prize for his contributions to electrocardiography.

37. Placement of electrodes in electrocardiography

39. Normal ECG ECG interpretation Measurements Rhythm analysis
0.04 sec
ECG interpretation
Measurements
Rhythm analysis
Conduction analysis
Waveform description
Comparison with previous ECG (if any)

40. P wave: the sequential depolarization of the right and left atria
QRS complex: right and left ventricular depolarization
ST-T wave: ventricular repolarization
U wave: origin for this wave is not clear - but probably represents "afterdepolarizations" in the ventricles

41. PR interval: time interval from onset of atrial depolarization (P wave) to onset of ventricular depolarization (QRS complex)
QT interval: duration of ventricular depolarization and repolarization
ST segment: the time period between the end of the QRS complex and the beginning of the T wave,  during which each myocyte is in the plateau phase (phase 2) of the action potential 

42. Normal
Partial block
Complete block

43. Physiological properties of cardiac cells
Excitability
Autorhythmicity
Conductivity
Contractility
Electrophysiological properties
（电生理特性）
Mechanical property
（机械特性）

44. Excitability（兴奋性） Factors affecting excitability Resting potential
Threshold potential
Status of Na+ or Ca2+ channels

45. Hyperkalemia（高钾血症）
The QRS complexes may widen so that they merge with the T waves, resulting in a “sine wave” appearance. The ST segments disappear when the serum potassium level reaches 6 mEq/L and the T waves typically become tall and peaked at this same range. The P waves begin to flatten out and widen when a patient‘s serum potassium level reaches about 6.5 mEq/L; this effect tends to disappear when levels reach 7-9 mEq/L. Sinus arrest may occur when the serum potassium level reaches about 7.5 mEq/L, and cardiac standstill or ventricular fibrillation may occur when serum levels reach 10 to 12 mEq/L.

46. Periodic changes in excitability

48. Premature systole & compensatory pause
(extrasystole)

49. A 39-year-old lady presenting with frequent palpitations lasting a few months
A 39-year-old lady presents to you with frequent palpitations lasting a few months, which are not associated with dizziness, syncope or angina. She has enjoyed good health and is not on any medication or herbal medicine. She is a non-smoker and has no known diabetes, hypertension or hypercholesterolaemia. Her menses is regular and physical examination is unremarkable other than a few premature beats. This is her ECG.
Answers:
Ventricular premature beats are noted.

50. Premature ventricular beats unmask the P waves

51. Autorhythmicity（自律性）

52. Autorhythmicity SA node 100 times/min AV node 50 times/min
Bundle of His times/min
Purkinje fibers 25 times/min

53. Normal pacemaker（正常起搏点） SA node Latent pacemaker （潜在起搏点）
(Ectopic pacemaker [异位起搏点] under pathophysiological conditions)
AV node
Bundle of His
Purkinje fibers

54. The mechanisms of SA node to control latent pacemakers
Capture（夺获）
Overdrive suppression（超速抑制）

55. Factors Affecting Autorhythmicity
Maximal repolarization potential
Threshold potential
The rate of phase 4 spontaneous depolarization

56. Sinus Bradycardia（窦性心动过缓）

57. Conductivity（传导性）

58. Gap junction

59. Conducting velocity
SA node Atria A-V node
0.05 m/s 0.4 m/s ~0.05 m/s
His bundle Purkinje fiber Ventricle
1.2~2.0 m/s 2.0~4.0 m/s 1.0 m/s
Atrioventricular delay（房室延搁）: Asynchronization of atrial and ventricular depolarization to provide adequate cardiac output

60. Factors Affecting Conductivity
Structural factors
Diameter of cardiac cells
Gap junctions at Intercalated disk
Physiological factors
The velocity and amplitude of phase 0 depolarization
Excitability of adjacent region

61. First Degree AV Block
Definition: 1AVB is a rhythm in which the electrical impulse which leaves the SA node and travels through the atria, AV node, Bundle of His to purkininjie fibers is slowed down and takes longer than normal to arrive at its destination. The normal PR interval is seconds. A 1AVBT is greater than 0.20 seconds. The cause ranges from coronary heart disease, inferior wall MI's, hyperkalemia, congenital abnormalities, and medications such as quinidine, digitalis, beta blockers, and calcium channel blockers.

62. Second degree AV Block type 1 (Mobitz)
Definition: Second degree AV block is also known as Second Degree Type I, Mobitz I, or Wenckelbach. This arrhythmia is characterized by a progressive delay of the conduction at the AV node, until the conduction is completely blocked. This occurs because the impulse arrives during the absolute refractory period, resulting in an absence of conduction, and no QRS. The next P wave occurs and the cycle begins again. Possible causes are acute inferior wall myocardial infraction, digitalis, beta blockers, calcium channel blockers, rheumatic fever, myocarditis, or excessive vagal tone.

63. Second degree AV Block Type II
Mobitz II is characterized by 2-4 P waves before each QRS. The PR of the conducted P wave will be constant for each QRS. It is usually associated with acute anterior or anteroseptal myocardial infarction. Other causes are cardiomyopathy, rheumatic heart disease, coronary artery disease, digitalis, beta blockers, and calcium channel blockers. Mobitz II has the potential of progressing into a third degree heart block or ventricular standstill.

64. Third Degree -- Complete Block
A third degree atrial ventricular block is also know as a complete heart block artrioventricular block of 3degree AV block. It is a problem with electrical conduction. All electrical conduction from the atria are blocked at the AV junction, therefore, the atria and the ventricles beat independently from each other. This arrhythmia is dangerous because it significantly decreases cardiac output, and could lead to asystole. Possible causes: acute inferior and anterior myocardic infraction, coronary heart disease, excessive vagal tone, myocarditis, endocarditis, age, edema from heart surgery, and meditation toxicity from digitalis, beta blockers, calcium channel blockers.

65. ------------------------++++++++++++++++++++++++++++
Reentry （折返）Model
Reentry can take place within a small local region within the heart or it can occur, for example, between the atria and ventricles (global reentry). For reentry to occur, certain conditions must be met that are related to the following:
the presence of a unidirectional block within a conducting pathway;
critical timing;
the length of the effective refractory period of the normal tissue.

66. The End.