第一 · 节 心脏的生物电现象及节律性 兴奋的产生与传导 心肌组织的生理特性： 兴奋性 传导性 自律性 收缩性 心肌细胞的分类：

1. 第一·节 心脏的生物电现象及节律性 兴奋的产生与传导 心肌组织的生理特性：兴奋性 传导性 自律性 收缩性 心肌细胞的分类： 工作细胞（普通心肌）：心房肌细胞，心室肌细胞 自律细胞（特殊传导系统）：起搏（Ｐ）细胞，浦肯野细胞 二种细胞的比较: 兴奋性 传导性 自律性 收缩性 工作细胞 有 有 无 有 自律细胞 有 有 有 无

2. Electrical Activity of the Heart • OBJECTIVES • Explain the types of cardiac action potentials. • Define the ionic basis of cardiac action potentials. • Explain the temporal changes in cardiac excitability. • 心肌细胞的快反应动作电位和慢反应动作电位； • 心肌细胞的电生理特性（传导性和兴奋性）

3. 威廉 . 艾因特霍芬 （Willem Einthoven）        荷兰生理学家 威廉 . 艾因特霍芬 （ Willem Einthoven, 1860~1927 ） 因对心电图学 的 开创性工作和 无与伦比 的贡献 而 被誉为“心电图之父”，并于 1924 年获 诺贝尔生理学或医学奖。 Willem Einthoven

4. Cardiac Transmembrane Potentials are Prolonged The electrical behavior of cardiac cells differs considerably from that of nerve cells or of smooth or skeletal muscle ceils. in general, the durations of action potentials are much longer in cardiac cells than in nerve cells or in smooth or skeletal muscle cells. The action potentials differ substantially among various type of cardiac cells depending on the function and location of those cells.

5. the potential charge recorded from ventricular muscle cell Resting potential ：- 90 mV (interior is lower than that of the surrounding medium) Action potential: Phase 0 : the rapid upstroke of the action potential. depolarizes from -90mV to +20～30 mV; Phase 1：a brief period of partial repolarization +20 mV  0 mV, Phase 2：a plateau ( persists for about 0.2 second). It is main difference comparing with nerve and skeleton muscle cells.

6. Phase 3 ：repolarization This proceeds more slowly than dose depolarization (phase 0). Phase 4 : The interval from the completion of repolarization until the beginning of the next action potential.

7. Action potential occurs well before the contractile force attains its peak, and repolarization is completed well before the cell reaches its full resting value. The relaxation of the cardiac muscle takes place mainly during phase 4 of the action potential.

8. There Are Two Principal Types of Cardiac Action Potentials • Fast-response action potentials: occur in atrial and ventricular myocardiac fibers and specialized conducting fibers (Purkinje fibers) that exist mainly in the endocardiac surfaces of the ventricles. • Slow-response action potentials:occur in the sinoatrial (SA) node (SA), which is the natural pacemaker region of the heart; • and the atrioventricular (AV) node, which is the specialized tissue that conducts the cardiac impulse from the atria to the ventricles.

9. Comparing with the fast-response action potential: The resting membrane of slower-response is considerable less negative, about -50 mV; The slop of the upstroke (phase 0), the amplitude and overshoot of the action potentials are less; （amplitude of action potential and the rate of rise of the upstroke are important determinants of the conduction velocity).

10. Fast responses may change to slow responses under certain pathological conditions, for example, in coronary artery disease

11. The Cardiac Transmembrane Potential Dependends Mainly on K+, Na+, and Ca++ Each phase of the action potential is associated with a change in conductance to one or more ions. The Resting Potential Is Determined by Ionic Diffusion

12. After raising [K]o, the measured value of Vm approximates that predicated by the Nernst equeation for Km (equilibrium potential). The measured values are slightly less negative than those predicted by Nernst equation because of the small but finite gNa

13. The Fast Response Depends on Na+ Phase 0 is genesis of the upstroke Any stimulus that abruptly changes the resting membrane potential to a critical value (called the threshold 阈值) results in an action potential. The rapid depolarization (phase 0) is related almost exclusively to the influx of Na+ into the myocyte due to a sudden increase in gNa.

14. The amplitude of the action potential (the potential change during phase 0) varies linearly with the logarithm of [Na+]o, When [Na+]o is increased from about 20% of its normal value to about 150% of its normal value, the transmembrane potential at the peak of the action potential increases from about -20 mV to about +40 mV.

15. When the resting membrane potential, Vm, is suddenly changed from -90 mV to the threshold level of about -65 mV the properties of the cell membrane change dramatically. Na+ enters the myocyte through specific fast Na+ channels that exist in the membrane. These channels can be blocked by the puffer fish toxin, tetrodotoxin.

16. the m gate, tends to open the channel as Vm becomes less negative. Hence, this is called an activation gate. the h gate, close the channel as Vm becomes less negative. Hence, this is called an inactivation gate.

17. Regenerative The consequent change in Vm opens more m gates and augments the inward Na+ current. As Vm approaches about -65 mV, the remaining m gates rapidly swing open in the fast Na+ channels until virtually all the m gates are open Effective refractory period The h gates then remain closed until the cell has partially repolarized during phase 3, in this time the cell is in its effective refractory period, and it will not respond to further excitation. Recovered from inactivation Na+通道有三种状态，都是电压依赖性的： 备用 (-90 mV)  激活  失活

18. Phase 1 is genesis of early repolarization Two mechanisms are responsible for phase 1: • When a notch is not evidence, phase 1 reflects the inactivation of the fast Na+ channels. • In cells characterized by a notch, phase 1 reflects not only the inactivation of Na+ channels, but also activation of a specific K+ current (transient outward current [Ito].

20. Roderick MacKinnon 罗德里克.麦金农 Rockefeller University, Howard Hughes Medical Institute New York, NY, USA

23. For inactivation to occur, a positively charged inactivation particle (ball)has to pass through one of the lateral windows and bind in the hydrophobic binding pocket of the pore’s central cavity.Kv1.4, 2001

24. Phase 2 is genesis of the plateau • The principal movement of cations across the cell membrane during phase 2 are a net efflux of K+ and a net influx of Ca 2+ . • The relevant Ca2+ channels is L-type Ca2+ channels. A substantial amount of Ca2+enter the cardiac cells throughout the plateau as three reasons: gCa2+, Ca 2+ concentration, positive potential. • Plateau remains fairly constant • for about 100 to 300 ms.

25. Various medications and neuro-transmetters may influence the Ca2+ current in cardiac cells. • Epinephrine strengthen myocardial contraction by increasing Ca2+ influx. • Ca2+ channels antagonist diminish the level of Vm during the plateau and abridge the duration of plateau by altering the balance between Ca2+ influx and K+ efflux. 地尔硫唑

26. Phase 3 is genesis of final repolarization • when the efflux of K+ front the cardiac cell begins to exceed the influx of Ca2+ final repolarization stars. • At least three outward K+ currents (ito, ik, and ik1) contribute to the final repolarization (phase 3) of the cardiac cell.

27. The Slow Response Is Found in all Cardiac Cells • fast-response action potentials consist of four components: • an upstroke (phase 0); • an early, partial repolarization (phase 1); • a plateau (phase 2); • and a final repolarization (phase 3). • slow response action potentials • the upstroke is much more gradual, • the early repolarization (phase 1) is absent, • the plateau is less prolonged and less flat, • The transition from the plateau to the final repolarization is less distinct.

28. SA and AV nodes are normally slow-response fibers. • In such fibers, depolarization is achieved mainly by the influx of Ca++ through the Ca++ channels. • Repolarization is accomplished in these fibers by the inactivation of the Ca++ channels and by the increased K+ conductance through the iK1 and iK channels.

29. The Fast Response Underlies Rapid Conduction of the Cardiac Impulse The conduction velocity along the fiber varies directly with the amplitude of the action potential and with the rate of change of potential (dVm/dt) during phase 0. important factor which determine the conduction velocity. • the amplitude of the action potential, • the rate of change of potential (dVm/dt) during phase 0, • The level of the resting membrane potential：This factor influences the amplitude of the action potential and the slope of the upstroke. The Na+ Current Determines Conduction of the Fast Response

31. The Ca++ Current Determines Conduction of the Slow Response The threshold potential is about -40 mV for the slow response, and this response is much slower than it is for the fast response. The conduction velocities of the slow responses in the SA and AV nodes are about 0.02 to 0.1 m/sec. The fast-response conduction velocities are about 0.3 to 1 m/sec for myocardial cells, and the velocities are about 1 to 4 m/secfor the specialized conducting (Purkinje) fibers in the ventricles.

32. Fast responses may change to slow responses under certain pathological conditions, for example, in coronary artery disease。

33. Cardiac Excitability Is Determined by the Availability of Na+ and Ca++ Currents Na+ channel activation and inactivation induced refractory period （不应期）: Effective refractory period:（有效不应期） The internal from the beginning of the action potential until the time the fiber can conduct another action potential. • from the beginning of phase 0 to the time in phase 3 at which Vm has reached about -50 mV (c to d).

34. At about this value of Vm, the electrochemical m and h gates for many of the fast Na+ channels have been reset.

35. Relatively refractory period: during period (d to e), an action potential may be evoked but only when the stimulus is stronger than that which elicits a response during phase 4. 图4-11 心肌细胞动作电位与兴奋性的变化 A. 在复极化的不同时期给予刺激所引起的反应 （a 为局部反应，b、c 和 d 为 0 期去极化速度和幅度都减小的动作电位） B. 用阈值变化曲线表示心肌细胞兴奋后兴奋性的变化

36. Premature systole and compensatory pause Premature systole(期前收缩): Compensatory pause(代偿间隙):

37. Ca++ channel generates the slow response: post-repolarization refractoriness: In slow-response fibers, the relative refractory Period frequently extends well beyond phase 3 . Even after the cell has completely repolarized, it may be difficult to evoke a propagated response for some time.

38. Natural Excitation of the Heart Objectives • Discuss the basis of automaticity. • Describe the spread of excitation of the heart. • Describe the components of the electrocardiogram

39. Automaticity: the ability to initiate a heartbeat Rhythmicity: the frequency and regularity of such pacemaking activity are intrinsic to cardiac tissue Natural pacemaker:the natural pacemaker cells are located in the SA nodein the mammalian heart; Ectopic pacemakers : Other regions of the heart that can initiate beats under special circumstances are called ectopic pacemakers. Ectopic pacemakers may become dominant when (1) their own rhythmicity is enhanced, (2) The more rhythmic pacemakers are depressed, (3) all conduction pathways are blocked.

40. The Sinoatrial Node Is the Natural Pacemaker of the Heart In adult humans, the SA node is about 8 mm long and 2 mm thick, and it lies posteriorly in the groove at the junction between the superior vena cava and the right atrium • small, round cells，it are probably the pacenraker cells. • slender, elongated cells, which are probably conduct the impulses to nodal margins • transmembrane action potential of the pacemaker cell in the SA node are characteristic of the slow response.

41. The principal distinguishing feature of an automatic fiber in the SA node (as in all automatic fibers) resides in phase 4. • The automatic cell in the heart displays a gradual diastolic depolarization (pacemaker potential) during phase 4.

42. The firing frequency of an automatic cell is varied by • changing the slope of the slow diastolic depolarization • the maximum negativity during phase 4 • the value of the triggering threshold

43. Through the release of acetylcholine, increased • parasympathetic activity diminishes the heart rate by reducing the slope and by increasing the maximum negativity of slow diastolic depolarization. • Changes in the firing threshold occur in response to certain medications and to changes in the ionic composition of the myocardial interstitial fluid.

44. fluxes of K+, Ca++ , and Na+ underlieautomaticity In the SA node, the slow diastolic depolarization is mediated by changes in at least three ionic currents: • an inward funny" current (if), • an inward Ca++ current (iCa), • an outward K+ current (iK) . if is carried mainly by Na+. It is activated as the membrane potential becomes more negative than about -50 mV during repolarization The more negative the membrane potential, the greater of if .

45. iCa is activated toward the end of phase 4 (about -55 mV). The influx of Ca++ accelerates repolarization, which quickly leads to the upstroke of the action potential. The efflux of K+ tends to oppose the depolarizing effects of if and iCa. The outward current iKdecays steadily throughout phase 4 because of its gradual inactivation. The diminishing of outward iK thus contributes to the slow diastolic depolarization.

46. The ionic basis for automaticity in the AV node pacemaker cells resembles that in the SA node cells. • For automaticity in Purkinje fibers, the Ca++ current does not contribute the slow diastolic depolarization . • Hence the slow diastolic depolarization in Purkinje fibers is mediated by the balance between the if (x), and the gradually diminishing iK (y) • .

47. The properties of automaticity in difference cardiac tissue SA node> AV node > Purkinje fibers 90~100次/分 40~60次/分 15~40次/分 Overdrive suppresses automaticity • The automaticity of pacemaker cells is suppressed temporarily after they have been driven at a critically high frequency. This phenomenon is known as overdrive suppression. • The mechanism responsible for overdrive suppression involves the membrane pump (Na+-K+-ATPase) . This enhanced activity of the Na+ pump hyperpolarizes the cell membrane because there is a net loss of cation from the cell interior. (sick sinus syndrome )

48. Atrial Muscle Conducts the Cardiac impulse from the Sinoatrial Node to the Atrioventricular Node From the SA node, the cardiac impulse spreads radially throughout the right atrium along ordinary atrial myocardial fibers, at a conduction velocity of 1 m/sec. A special pathway, the anterior interatrial myocardial band (Bachmann's bundle), conducts the impulse from the SA node directly to the left atrium.

49. Atrioventricuiar Node Connects the Atria to the Ventricuiar Conducting System The AV node in adult human is 22 mm long, 10 mm wide, and 3 mm thick. The AV node is divided into the following functional regions: (1) the A-N region, (2) the N region, (3)the N-H region, in which tile nodal fibers gradually merge with the bundle of His。 The conduction velocity is actually slower in the N region than in the AN regionthe conduction velocity is about 0.05 m/sec.. The principal delay in the passage of the impulse from the atria to the ventricles occurs in the AN and N regions of the AV node.

50. An abnormal prolongation of the AV conduction time is called first-degree AV block.