Cardiac physiology

Question 1

Define the absolute refractory, effective refractory, relative refractory, and supranormal periods of the cardiomyocyte action potential and relate them to the phases of the AP.

Answer 1

• absolute refractory period
  
  • No new stimulation will cause further excitation, regardless of the strength of the stimulation. Extends from beginning of phase 0 to end of phase 2
• effective refractory period
  
  • Stimulation may cause a localized AP, but not one strong enough to propagate further. Includes the ARP + the early part of phase 3
• Relative refractory period
  
  • A strong enough signal can cause a new action potential. Higher rates possible in atrial cells. Extends from mid-to-late phase 3.
• Supranormal period
  
  • A less-than-normal signal can cause depolarization due to disturbed ion concentrations at end of phase 3

Question 2

Which chambers can maintain a greater rate of depolarization during arrythmia, the atria or ventricles?

Answer 2

the atria

Atrial cells have a significantly shorter refractory period than ventricular cells

Question 3

Decribe the events of phase 4 of the cardiomyocyte action potential in terms of:

• transmembrane potential
• ion currents/channels
• correlation to the cardiac cycle

Answer 3

• transmembrane potential
  
  • this is the “resting membrane potential” which is maintained at a relatively constant -90mV
• ion currents/channels
  
  • RMP is maintained by the Na/K pump and the inward potassium rectifier channel (I_K1)
• correlation to the cardiac cycle
  
  • Myocardium is relaxed. Diastole. Corresponds to TP segment on the ECG

Question 4

Which phase of the cardiomyocyte action potential is maintained by the sodium/potassium pump?

Answer 4

phase 4: the resting membrane potential

Question 5

Decribe the events of phase 1 of the cardiomyocyte action potential in terms of:

• transmembrane potential
• ion currents/channels
• correlation to the cardiac cycle

Answer 5

• transmembrane potential
  
  • After sodium channels close, potential quickly returns form positive range to ~0mV
• ion currents/channels
  
  • Outward flow of potassium through I_to (transient outward) channels allows for return to 0 voltage. No sodium or calcium cahnnels are open
• correlation to the cardiac cycle
  
  • Peak cardiomyocyte depolarization (mid-QRS or P-wave in case of atria)

Question 6

Decribe the events of phase 2 of the cardiomyocyte action potential in terms of:

• transmembrane potential
• ion currents/channels
• correlation to the cardiac cycle

Answer 6

• transmembrane potential
  
  • Potential enters a “plateau phase”, persisting at 0mV
• ion currents/channels
  
  • Delayed, rectifier potassium currents (I_Ks and I_Kr) are balanced by slow, long, inwards calcium current (I_Ca.L). Note that I_Ca.L channels open in phase 0 but the effect is most pronounced in phase 2
• correlation to the cardiac cycle
  
  • Calcium influx leads to calcium-induced calcium release from sarcoplasmic reticulum. Causes excitation-contraction coupling and systole (PR-segment or ST segment)

Question 7

Describe the dominant ion currents during phase 4, 0, and 3 of the cardiac pacemaker action potential.

Answer 7

• Phase 4
  
  • Gradual, spontaneous depolarization due to the “pacemaker potential”, or I_f. Overwhelms the ability of Na/K pump to maintain RMP and leads to automaticity
• Phase 0
  
  • Depolarization after reaching threshold of ~-40mV due to opening of L-type calcium channels (I_Ca.L)
• Phase 3
  
  • Repolarization due to slow inactivation of L-type calcium channels and opening of potassium rectifier channels (I_Ks and I_Kr)

Question 8

Describe 4 major differences between the cardiac pacemaker and cardiomyocyte action potentials

Answer 8

1. Pacemaker cells have a significantly reduced RMP (-60mV vs. -90mV)
2. Pacemaker cells exhibit a “pacemaker current” (I_f) during phase 4, causing automaticity
3. Phase 0 of the pacemaker AP is much more gradual than in cardiomyocytes due to pacemakers relying entirely on L-type Ca-channels for depolarization, rather than sodium.
4. Pacemaker cells lack a phase 1 or 2 of the action potential. depolarization is followed by immediate repolarization (no plateau)

Question 9

Describe transmembrane ion gradients of sodium, potassium, and calcium in the resting cardiomyocyte

Answer 9

• Excess of sodium and clacium in the eternal environment
• Excess of potassium intracellularly

Question 11

Decribe the events of phase 0 of the cardiomyocyte action potential in terms of:

• transmembrane potential
• ion currents/channels
• correlation to the cardiac cycle

Answer 11

• transmembrane potential
  
  • from resting potential (~-90mV), stimulation causes depolarization to the threshold potential (~-70mV), leading to rapid depolarization up to ~+20mV
• ion currents/channels
  
  • Upon reaching threshold, votlage-gated sodium channels open, allowing rapid influx of sodium (I_Na). Voltage-gated Na channels are only briefly open, closing at the end of phase 0
• correlation to the cardiac cycle
  
  • Correlates to pre-systolic depolarization (early QRS)

Question 12

Decribe the events of phase 3 of the cardiomyocyte action potential in terms of:

• transmembrane potential
• ion currents/channels
• correlation to the cardiac cycle

Answer 12

• transmembrane potential
  
  • “repolarization phase” occurs as membrane potential returns from 0 mV to -90mV
• ion currents/channels
  
  • L-type Calcium channels (I_Ca.L) which opened in phase 0 and began to inactivate in phase 2 are no longer able to match efflux of potassium through rectifier channels, causing a return to negative potential. Normal transmembrane gradients are restored by the Na+/K+ pump
• correlation to the cardiac cycle
  
  • Repolarization corresponds to the T-wave (atrial repolarization normally not seen on ECG) and signals early diastole

Question 13

Which of the following are effects of beta-adrenergic (beta-1) stimulation of the heart?

• Increased heart rate
• Increased contractility
• Increased relaxation
• Increased conduction velocity thorugh conductive tissue

Answer 13

All of them!