Circulatory Physiology and Bioelectrical Activity of Cardiac Myocytes

1. 郑 煜（Zheng Yu） Department of Physiology West China School of Preclinical and Forensic Medicine Sichuan University Tel: 8550 2389 E-mail: yzheng@scu.edu.cn QQ: 1595486138 华西校区 逸夫楼 4-19 循环生理学课件网址： http://cc.scu.edu.cn/G2S/Template/View.aspx?courseType=1&courseId=43&topMenuId=118511&menuType=1&action=view&type=&name=&linkpageID=118560

2. 循环生理学 Circulatory Physiology 心血管生理学 Cardiovascular Physiology or

3. 教材和参考书 姚泰主编 生理学（八年制规划教材） 第二版，人民卫生出版社，2010。 朱大年主编 生理学（五年制规划教材） 第八版，人民卫生出版社，2013。 Guyton & Hall Textbook of Medical Physiology 12 Ed, Saunders, 2011.

4. William Harvey 1578-1657 1628 实验生理学的起源 !!! 现代医学的开端 !!!

5. 2 parts and 2 circulations

6. Main Topics to be Discussed Bioelectrical Activity and Physiological Properties of Cardiac Myocyte （心肌细胞的生物电活动和生理特性） Heart as a Pump （心脏的泵血功能） Functions of Blood Vessels （血管的功能） Regulation of Cardiovascular Activity （心血管功能的调节） Coronary Circulation （冠脉循环）

7. Part One 心肌细胞的 生物电活动和生理特性 (Bioelectrical Activity and Physiological Properties of Cardiac Myocyte)

8. I. 心肌细胞的生物电活动 （Bioelectrical Activity） 自律细胞 工作细胞

9. 1 1 2 2 0 3 0 3 0 3 0 3 4 4 -70 4 4 -90 Purkinje C. Node Region Atrial M. Ventricular M. Sinus Node A-V Node (not Node Region) Skeletal M.C. Neuron Autorhythmic Nonautorhythmic Fast Response C. PurkinjeAtrial Muscle Ventricular M. Slow Response C. Sinus N. Node Region A-V N. (not Node Region) Autorhythmic Nonautorhythmic Fast Response C. PurkinjeAtrial Muscle Ventricular M. Slow Response C. Sinus N. Node Region A-V N. (not Node Region) Sinus Node A-V Node (not Node Region) Atrial M. Ventricular M.

10. 1.心室肌细胞的生物电活动 1 2 0 mV 3 0 4 ﹣90 mV Pattern Mechanism Permeability of cell membrane to ions Driving force (electro-chemical gradient)

11. [K+]i [K+]o K+ outward flow EK+ Higher PK+ (IK1) Na+ inward flow background current 1) Resting Potential– 90 mV 1 2 0 mV 3 0 4 ﹣90 mV electrogenic Na+-K+ pumppump current

12. 1 2 0 mV 3 0 4 ﹣90 mV 0 depolarization 1 initial rapid repolarization Phase 2 plateau (slow repolarization) 3 final rapid repolarization 4 polarization (“resting”) spike 2) Action Potential

13. Phase 0 Phase 0: rapid depolarization –90 ～ +30 mV 200 ～ 400 V/s 1 ～ 2 ms (fast response potential) Na+ channels open → Na+ flow in (INa) → ENa+ [Na+]o [Na+]i blocked by TTX

14. Phase 1 Phase 1: initial rapid repolarization + 30 ～ 0 mV 10 ms Na+ channels inactivation K+ channels open → K+ flow out → transient outward current (Ito) activated at –30 mV blocked by 4-aminopyridine

15. Phase 2: around 0 mV plateau (phase of slow repolarization) 100 ～ 150 ms Phase 2 L-type Ca++ channels open Ca++ flow in ( ICa-L ) at –30 ～ –40 mV slow blocked by Mn++ IK ↑ (activated at –40 mV dep. , inactivated at –40 ～ –50 mV rep.) IK1 ↓ (inward rectification)

16. final rapid repolarization 0 ～ – 90 mV 100 ～ 150 ms Phase 3 Phase 3: K+flow outward (IK )till –50 mV IK1recover gradually

17. Phase 4: – 90 mV 1 0 mV IK1 recovered Na+ - K+ pump (3Na+ outward, 2K+ inward) (Na+ - K+ pump current) Na+ - Ca++ exchanger (3Na+ inward, 1Ca++ outward) (Na+ - Ca++ exchange current) Ca++ pump (a few Ca++ outward) (Ca++ pump current) 2 3 0 4 ﹣90 mV Membrane more active

18. Summary 30 mV (10 ms) (100-150 ms) (1-2 ms) (100-150 ms) 1 2 -90 mV 0 outside 3 K+ inside 4 4 K+ 4 0 1 2 3 4 Ca2+ Ca2+ K+ K+ K+ Na+ 2K+ 3Na+ INa Ito IK IK1 IK1 IK ICa-L INa+ - K+ pump INa+ - Ca++ exchange K+ Ca2+ 3Na+ ICa++ pump

19. 2.窦房结起搏细胞的生物电活动 （Sinus Pacemaker Cell）

20. 1 2 0 mV 3 0 -70 mV 4 -90 mV 0 mV 0 mV 0 3 3 0 -40 mV 4 -40 mV -70 mV 4 -70 mV 1) 特点（Properties） 3 phases (no phases 1 and 2) lowermaximal repolarization p. (-70 mV) lower threshold potential (-40 mV) lower amplitude (70 mV) longer duration of depolarization (7 ms) slower velocity of depolarization (10V/s) automatic depolarization (0.1 V/s)

21. L-type Ca++ channels open (ICa-L) 2) 机制（Mechanism） Phase 0:

22. K+ channels open (IK) Phase 3:

23. IK activated ICa-T IK inactivated ICa-L If Phase 4: IK decreases gradually If(funny current) (Na+, a few K+) (pacemaker current) ICa-Tincreases

24. 0 mV 0 3 4 –40 mV –70 mV Ca2+ (ICa-L) Na+ (If) outside K+(IK) inside Ca2+ (ICa-T) Summary

25. Importance of maintenance of ions concentration in the activity of cardiac cells

26. II. 心肌细胞的生理特性 （Physiological Properties） Electrophysiological Properties Excitability（兴奋性） Autorhythmicity（自动节律性） Conductivity（传导性） Mechanical Property Contractility（收缩性）

27. 工作细胞 兴奋性  自律性  传导性  收缩性  自律性细胞 兴奋性  自律性  传导性  收缩性 

28. 1) Factors affecting excitability State of ion channels resting ↓ activation ↓ inactivation ↓ reactivation 1.兴奋性（Excitability） RP or maximal repolarization potential Threshold potential

29. 2) Changes in Excitability during Excitation ERP (1) Effective Refractory Period (ERP)（有效不应期） Phase 0 ~–60 mV (Rep) Excitability 0 Absolute Refractory Period（绝对不应期） Phase 0 ~ –55 mV rep. Local Response Period （局部反应期） – 55 ~ –60 mV rep. Local response

30. ERP RRP (2) Relative Refractory Period (ERP)（相对不应期） –60 ~ –80 mV rep. Excitability 

31. ERP RRP SNP (3) Supranormal Period (SNP)（超常期） –80 ~ –90 mV rep. Excitability 

32. ERP 3) Relation of Changes in Excitability to Mechanical Contraction ERP特别长，直到机械收缩的舒张早期。 (1) 特点： (2)意义： 保证舒缩交替进行，不会发生强直收缩，以利于血液充盈和射血。 骨骼肌呢？

33. 4) Premature Systole and Compensatory Pause （期前收缩与代偿间歇） Compensatory Pause Premature Systole (Extrasystole) Sinus AP Extra St.

34. 3) Autorhythmic Tissues in the Heart the special conduction system of the heart except for the node region of the A-V node 2.自动节律性（Autorhythmicity） 1) Definition the ability of the cardiac myocyte to produce automatically rhythmic excitation without external stimuli 2) Mechanism automatic depolarization in phase 4

35. Normal pacemaker — Sinus rhythm Ectopic pacemaker Ectopic rhythm Sinus node—100impulses/min A-V node —50impulses/min Bundle of His —40 impulses/min Purkinje F —25impulses/min Preocupation (Capture) Overdrive Suppression

36. 4) Factors affecting autorhythmicity • velocity of automatic depolarization • in phase 4 (2) maximal repolarization potential (3) threshold potential

37. Sinus rhythm 窦性心律 Ectopic rhythm 异位心律 Arrhythmia 心律失常 • Tachycardia 心动过速 • Bradycardia 心动过缓 • Cardiac arrest 心跳骤停 • Coupled rhythm 二联律 • Trigeminal rhythm 三联律 • … …

39. Artificial Pacemaker （人工起搏器）

40. 3.传导性（Conductivity） Principle of conduction local current in a single cell

41. Na+ Na+ Na+ 蛋白亚单位 Na+ Na+ Na+ 细胞膜 like a single cell for atria or ventricles 连接蛋白 （connexin） 连接子 （connexon） 与骨骼肌比较

42. 1) Conduction pathway

43. Sinus node Atria (1 m/s) A-V node (0.02-0.05 m/s) Bundle of His Purkinje F. (1.5-4 m/s) Ventricle (1 m/s) 2) Properties and their significances (1) fast in the atrial and ventricular muscles, but very slow in the A-V node functional syncytium（功能合胞体） important for pumping blood

44. Properties and their significances of conduction (2) atrioventricular delay（房-室延搁） important for a successive contraction of atria and ventricles and then for the pumping function of the heart

45. 3) Factors affecting conductivity (1) Structural property diameter of cell number of gap junction (2) Velocity and amplitude of depolarization in phase 0 depending on the open velocity and number of Na+ channels (efficiency of Na+ channels) and affected by resting potential (3) Excitability of adjacent cell or adjacent portion of membrane of a cell RP, TP, state of ion channels

46. 4.收缩性的特点 （Properties of Contractility） Ca++ induced Ca++ release (CICR) in cardiac cell（钙诱导钙释放） atria or ventricles as a functional syncytium (“all or none”) no tetanus

47. Summary about Bioelectrical Activity and Physiological Properties

48. Part Two 心脏的泵血功能 （The Heart as a Pump）

49. Topics to be discussed in this part : Cardiac Cycle Mechanism of Pumping Blood Evaluation of Pumping Function Factors Affecting Pumping Function Heart Sounds

50. I.心动周期（Cardiac Cycle） 1. 定义（Definition） the period from the beginning of heart contraction to the beginning of next, consisting of a period of contraction called systolefollowed by a period of relaxation calleddiastole