CHAPTER 4CIRCULATION Professor Pan Jing-yun Department of Physiology
Differences of AP configurations in different regions of the heart. • Fast response potential • Fast response cells: atrium cell and ventricle cells – working myocardium. • Fast response automatic cells: Purkinje fiber and bundle of His. • Slow response potential • Slow response cells: S–A node and A–V node.
Basic concepts Depolarization –– cations influx ---- Na+, Ca+inward current Repolarization –– cations efflux ---- K+ outward current Hyperpolarization: Vm → more negative than RMP Net current: inward ＜ outward repolarization inward ＞ outward depolarization inward ＝ outward no change in Vm
⒈ Typical features Resting membrane potential (RMP) Action potential (AP)Phase o (rapid depolarization)Phase 1(rapid initial repolarization)Phase 2 (plateau)Phase 3 (rapid late repolarization)Phase 4 (resting membrane potential)
⒉ Ionic basis for RMP and AP of working myocardium a. Ionic concentration differences cross membrane b. Permeability to ions (conductance)
⑴ Ionic basis for RMP K+ permeability ↑, [K+]i＞ [K+]o RMP ≌ K+ equilibrium potential
⑵ Ionic basis for APPhase 0 (depolarization) Stimulation → partial depolarization → threshold potential (-70mV) →Na+ Ch. opening →Na+ influx into cell down electrochemical gradient → Vm less negative→0 mV → +30 mV (overshoot)
Features of fast Na+ channel (1). Activated and inactivated very fast. Speed of depolarization: 120- 200 V / s; Fast response potential Fast response cell Fast channel
Regenerative process: depolarization caused by Na+ influx induces more Na+ Ch. to open and Na+ influx. At same time, K+conductance falls and keeps Vm at depolarization state.
(2). Voltage dependent Activation -70mV Inactivation +30mV Recovery to reopen from -60mV (3). Blocked by TTX
Phase 1 (rapid repolarization) (1) Na+ Ch. is inactivated at +30mV (2) Transient outward current (Ito) K+outward current, blocked by tetraethylammonium(TEA) and 4-aminopyridin.
Phase 2 (plateau) Ca2+ Ch. activation at –40mV → Ca 2+ influx → Ca2+ inward current IK Ch. Is activated slowly at phase o K+ slowly efflux → K+ outward current Inward Ca2+ current = outward K+ current at early stage of plateau Inward current ＜ outward K+ current at late plateau, Vm → more negative → repolarization
Close of IK1 Ch. at phase o and plateau prevents membrane potential from rapid repolarization Phase 2 is the integration of inward Ca2+current and outward K+current. The features of Ca2+ channel:
(1).Slow channel, slow inward current, slow activation and inactivation and reactivation (2).Voltage dependent: Activated at –40mV, inactivated at 0mV (3).Blocked by Mn2+ and verapamil (4).Low specialty: permeability to Na+ also.
Phase 3 (late repolarization) Ca2+ channel is inactivated. ↑K+ efflux via IK channel ↑K+ efflux via IK1 channel →↑outward K+ current → Vm → more and more negative → RMP.
Phase 4 (resting stage) During Phase 1-3, Na+, Ca2+ and K+ imbalance outside and inside cell. During Phase 4, Na+, Ca2+ efflux against concentration gradient; K+ influx against concentration gradient .
Na+-K+ pump: 3 Na+ out and 2 K+ in Na+-Ca2+ exchange – antiport 1 Ca2+ out and 3 Na+ in dependent of Na+ concentration difference inside and outside cell. Ca2+ pump: Ca2+ out of cell.
II. Transmembrane potential of rhythmic cell and their ionic basis Automatic fast response cell –– Purkinje cell. Automatic slow response cell in S-A node and A-V node
Spontaneous, phase 4 depolarization the cause of automaticity pacemaker potential ⑴ Maximal repolarization potential at the end of phase 3. ⑵ Phase 4 depolarizes automatically and slowly.
⑶ When depolarization reaches threshold level, excitation (AP) appears. .
(1) Features of P cell in S-A node a. Slow depolarization of phase 0, 7ms, 10V／s ,magnitude 70mV Due to Ca2+ channel opening, blocked by Verapamil or Mn2+.b. No distinct phase 1 and phase 2
c. Smaller overshoot (+15mV)d. Maximum diastolic potential –70mV, firing level – 40mV.f. Repolarization –– K+ outward current.g. Faster spontaneous phase 4 depolarization.
a. Inward current, if b. Inward Ca2+ current, iCa c. Outward K+ current, iK
a. Inward current, if Features of if: (a) Carried by Na+, blocked by Cs, but not TTX (b) Activation at -60mV,full activation at –100mV (c) Noradrenalin → ↑ifAcetylcholine →↓if
b. Inward Ca2+ current, iCaActivation at -55mV Noradrenalin → ↑ifAcetylcholine →↓ifBlocked by Ca ch.blockade
With time the inward current (iCa，if ） ＞ outward current（Ik), causing phase 4 diastolic depolarization to reach firing level results in a new action potential.
2. Ionic basis of AP of rapid response automatic cells as the same as that of AP of working cells except phase 4.
Ionic basis of spontaneous phase 4 depolarization in fast response cell-Purkinje cell
(1) Gradual increase in inward current，if(2) Gradually diminishing outward K+ current, iK If＞ IK , depolarization →threshold potential → a new AP
III. Electrophysiological properties of cardiac muscle Excitability; Automaticity (autorhythmicity); Conductivity.
⒈Excitability and its affecting factors (1).Excitability: 1／threshold strength. Affecting factors: a.Excitation is caused by depolarization reaching threshold level, so affecting factors are:
1. Excitability and its affecting factors 1).Excitability index: 1／threshold strength.Affecting factors: a. Excitation is caused by depolarization reaching threshold level, so affecting factors are: