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LIU Chuan Yong 刘传勇 Institute of Physiology Medical School of SDU Tel 88381175 (lab) 88382098 (office) Email: li

LIU Chuan Yong 刘传勇 Institute of Physiology Medical School of SDU Tel 88381175 (lab) 88382098 (office) Email: liucy@sdu.edu.cn Website: www.physiology.sdu.edu.cn. Section 2. Electrophysiology of the Heart. CARDIAC ELECTROPHYSIOLOGY. Two kinds of cardiac cells.

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LIU Chuan Yong 刘传勇 Institute of Physiology Medical School of SDU Tel 88381175 (lab) 88382098 (office) Email: li

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  1. LIU Chuan Yong 刘传勇 Institute of Physiology Medical School of SDU Tel 88381175 (lab) 88382098 (office) Email: liucy@sdu.edu.cn Website: www.physiology.sdu.edu.cn

  2. Section 2 Electrophysiology of the Heart

  3. CARDIAC ELECTROPHYSIOLOGY

  4. Two kinds of cardiac cells 1, The working cells. Special property: contractility

  5. 2, Special conduction system including the Sinoatrial node, Atrioventricular node, Atrioventricular bundle (bundle of His), and Purkinje system. Special property: automaticity

  6. Transmembrane Potentials of Myocardial Cells

  7. Na+ ATP K+ Ions and Cells

  8. Na+ Cl- Cl- Cl- K+ K+ Na+ Cl- Cl- Na+ Na+ K+ K+ Na+ Cl- Cl- Cl- Cl- K+ Cl- K+ Cl- Na+ Cl- Cl- K+ Cl- Na+ Lipid bilayer membrane Na+ Cl- Cl- K+ A Cell 0 mV - X mV K+

  9. Equilibrium • The process of ions diffusing and changing the membrane voltage will continue • until the membrane potential attains a value sufficient to balance the ion concentration gradient. • At this point the ion will be “in equilibrium”. • What is this potential?

  10. The Nernst Potential An ion will be in equilibrium when the membrane potential is: where [X]o and [X]i are the external and internal concentrations of the ion; R, T, and F are thermodynamic constants such that (at 37 °C): The Nernst Potential

  11. For Example... • Typically, [K]o = 4 mM and [K]i = 140 mM • so VK = 61*log(4/140) = - 94 mV • i.e. a cell with these normal K concentrations and ONLY a K-selective ion channel will have a membrane potential of -94 mV • Likewise, [Na]o = 140 mM and [Na]i = 10 mM • so VNa = 61*log(140/10) = + 70 mV • i.e. a cell with these normal Na concentrations and ONLY a Na-selective ion channel will have a membrane potential of +70 mV

  12. 0 0 mv mv -90mv -90mv 0 mv -80mv ACTION POTENTIALS FROM DIFFERENT AREAS OF THE HEARTFast and Slow Response ATRIUM VENTRICLE SA NODE time

  13. ELECTROPHYSIOLOGY OF THE FAST VENTRICULAR MUSCLE AMP +20 1 To oscilloscope 2 0 3 0 mv Cardiac Cell 4 -90 0 300 t (msec)

  14. General description Resting potential: -90mv Action Potential Phase 0: rapid depolarization, 1-2ms Phase 1: early rapid repoarization, 10 ms Phase 2: plateau, slow repolarization, the potential is around 0 mv. 100 – 150ms Phase 3, late rapid repolarization. 100 – 150 ms Phase 4 resting potentials +20 1 2 0 3 0 mv 4 -90 0 300 t (msec)

  15. Ion Channels in Working Muscle • Essentially same in atrial and ventricular muscle • Best understood in ventricular cells

  16. Ion Channels in Ventricular Cells • Voltage-gated Na+ channels • Inward rectifier K+ channels • L-type Ca2+ channels • Several Voltage-gated K+ channels

  17. Cardiac Na+ Channels • Almost identical to nerve Na+ channels (structurally and functionally) • very fast opening (as in nerve) • has inactivation state (as in nerve) • NOT Tetrodotoxin sensitive • Expressed only in non nodal tissue • Responsible for initiating and propagating the action potential in non nodal cells

  18. +20 1 2 0 3 0 mv 4 -90 0 300 t (msec)

  19. Inward Rectifier (Ik1) Structure Note: No “voltage sensor” P-Region Extracellular Fluid M1 M2 membrane Inside H2N HO2C

  20. Inward Rectifier Channels 0 Ek

  21. Inward Rectification K+ K+ K+ K+ Mg2+ Mg2+ Extracellular solution Intracellular Solution K+ K+ K+ -80 mV -30 mV K+ K+

  22. Inward Rectifier Channels 0 Ek

  23. Role for Inward Rectifier • Expressed primarily in non nodal tissues • Sets resting potential in atrial and ventricular muscle • Contributes to the late phase of action potential repolarization in non nodal cells

  24. +20 1 2 0 3 0 mv 4 -90 0 300 t (msec)

  25. Inactivating K channels (ITO) “Ultra-rapid” K channels (IKur) “Rapid” K channels (IKr) “Slow” K channels (IKs) Cardiac Voltage-gated K Channels • All structurally similar to nerve K+ channels • ITO is an inactivating K+ channel- rapid repolarization to the plateau • IKur functions like nerve K+ channel- fights with Ca to maintain plateau • IKr, IKs structurally and functionally complex

  26. Cardiac Ca2+ Channels • L-type • Structurally rather similar to Na channels • Some functional similarity to Na channels • depolarization opens Ca2+ channels • Functionally different than Na channels • slower to open • very slow, rather incomplete inactivation • generates much less current flow

  27. Role of Cardiac Ca2+ Channels • Nodal cells • initiate and propagate action potentials- SLOW • Non nodal cells • controls action potential duration • contraction

  28. Ca2+CHANNEL BLOCKERS AND THE CARDIAC CELL ACTION POTENTIAL DILTIAZEM 地尔硫卓 ACTION POTENTIAL CONTROL 10 µMol/L 30 µMol/L 10 30 CONTROL 10 FORCE 30 TIME

  29. 0 0 mv mv -90mv -90mv Ion Channels in Atrial Cells • Same as for ventricular cells • Less pronounced plateau due to different balance of voltage-gated Ca2+ and K channels ATRIUM VENTRICLE

  30. OVERVIEW OF SPECIFIC EVENTS IN THE VENTRICULAR ACTION POTENTIAL

  31. Activation & Fast Inactivation

  32. Na+ Na+ m m m A B h h -65mv -90mv Na+ Na+ m m C D h h 0mv +20mv Na+ m E h +30mv PHASE 0 OF THE FAST FIBER ACTION POTENTIAL Chemical Gradient Electrical Gradient

  33. Inactivating K channels (ITO) “Ultra-rapid” K channels (IKur) “Rapid” K channels (IKr) “Slow” K channels (IKs) Voltage-gated Na Channels Voltage-gated Ca Channels 200 msec IK1 Ion Channels in Ventricular Muscle 0 Ventricular muscle membrane potential (mV) -50

  34. Ion Channels in Ventricular Muscle Current Na Current Ca Current IK1 ITO IKur IKr IKs

  35. 2. Transmembrane Potential of Rhythmic Cells

  36. Ion Channels in Purkinje Fibers • At phase 4, the membrane potential does not maintain at a level, • but depolarizes automatically – the automaticity • (Phase 0 – 3) Same as for ventricular cells • (Phase 4) Plus a very small amount of If (pacemaker) channels

  37. Activated by negative potential (at about -60 mv during Phase 3) • Not particularly selective: allows both Na+ and K+

  38. The SA node cell • Maximal repolarization (diastole) potential, –70mv • Low amplitude and long duration of phase 0. It is not so sharp as ventricle cell and Purkinje cell. • No phase 1 and 2 • Comparatively fast spontaneous depolarization at phase 4 A, Cardiac ventricular cell B, Sinoatrial node cell

  39. SA Node Action Potential Voltage-gated Ca+2 channels Voltage-gated K+ channels 0 SA node membrane potential (mV) No inward-rectifier K+ channels -50 If or pacemaker channels 200 msec

  40. SA Node Cells Current Ca Current K currents If (pacemaker current)

  41. CAUSES OF THE PACEMAKER POTENTIAL K+ if iCa OUT IN iK Na+ Ca++

  42. LOOKING AT THE PACEMAKER CURRENTS voltage iK if ionic currents iCa

  43. AV Node Action Potentials • Similar to SA node • Latent pacemaker • Slow, Ca+2-dependent upstroke • Slow conduction (delay) • K+-dependent repolarization 0 AV node membrane potential (mV) SA node -50 AV node 200 msec

  44. Fast and slow response, rhythmic and non-rhythmic cardiac cells • Fast response, non –rhythmic cells: working cells • Fast response, rhythmic cells: cells in special conduction system of A-V bundle and Purkinje network. • Slow response, non-rhythmic cells: cells in nodal area • Slow response rhythmic cells: S-Anode, atrionodal area (AN), nodal –His (NH)cells

  45. II Electrical Properties of Cardiac Cells Excitability, Conductivity and Automaticity

  46. 1. Excitability of Cardiac Muscle

  47. (1) Refractory Period +25 1 RRP 0 -25 2 3 0 -50 Transmembrane Potential 4 ARP -75 -100 -125 0 0.1 0.2 0.3 Time (msec) • Absolute Refractory Period – regardless of the strength of a stimulus, the cell cannot be depolarized. • Relative Refractory Period – stronger than normal stimulus can induce depolarization.

  48. Refractory Period • Absolute Refractory Period (ARC): Cardiac muscle cell completely insensitive to further stimulation • Relative Refractory Period (RRC): Cell exhibits reduced sensitivity to additional stimulation

  49. Na+ Channel Conformations Another Non-conducting conformation (a while after more depolarized potentials) Non-conducting conformation(s) (shortly after more depolarized potentials) Conducting conformation (at negative potentials) Open Inactivated Closed Outside IFM Inside IFM IFM

  50. Refractory Period • The plateau phase of the cardiac cell AP increases the duration of the AP to 300 msec, • The refractory period of cardiac cells is long (250 msec). • compared to 1-5 msec in neurons and skeletal muscle fibers.

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