Cardiac Electrophysiology

Question 1

Differentiate between the electrocardiogram and cardiac action potential.

Answer 1

• Cardiac Action Potential: 3 types
  
  • Ventricular
  • Atrial
  • Nodal
  • These action potentials occur in distinct regions of the heart
• ECG
  
  • The ECG is an extracellular recording of instantaneous, heart electrical activity
    
    • Measures potentials from the ENTIRE heart via electrodes on the surface of the body
    • Recorded ECG potential is a result of an instantaneous vector sum of the changing polarizations of all cells in the ENTIRE heart
• Differences:
  
  • Previous recordings were intercellular
    
    • Measured potentials from an electrode inside a single cell
  • ECG is an extracellular recording from many cells

Question 2

Identify the electrical phases (0 through 4) of ventricular and nodal action potentials.

Answer 2

• Cardiac action potentials are divided into phases: 0-4
  
  • Ventricular and atrial action potentials have all 5 phases
  • Nodal action potential lacks phases 1 and 2
• Phase 4:
  
  • Resting potential in ventricular and atrial cells
  • Pacemaker potential in nodal cells
• Phase 0:
  
  • Rapid depolarization at the start of the action potential
  • Present in ventricular, atrial and nodal cells
  • Responsible ion is different in nodal cells
• Phase 1:
  
  • Brief, partial repolarization of Ventricular and Atrial action potentials
  • NOT present in nodal action potentials
• Phase 2:
  
  • Plateau of the ventricular action potential
  • Abbreviated in the atrial action potential
  • NOT present in the nodal action potential
• Phase 3:
  
  • Repolarization that returns membrane potential to resting/pacemaker level
  • Present in ventricular, atrial and nodal cells

Question 3

Ventricular AP: Phase 4

Answer 3

• Resting diastolic membrane potential
• produced mainly by a non-gated, inwardly rectifying K+ channel that behaves as if it was voltage-gated
• Stabilizes resting Em near EK
• The inward rectifying iK1 potassium current through the channel -Is primarily responsible for the resting potential
• After depolarization Mg2+ and polyamines partially block the channel and decrease K+ permeability
  
  • Easier for other currents (Na and Ca) to depolarize

Question 4

Ventricular AP: Phase 0

Answer 4

• Initial action potential depolarization
• Produced by Voltage activated Na+ channels: “fast sodium channels”
• When activated by depolarization they open and close increasing and then decreasing the Na+ permeability automatically.

Question 5

Ventricular AP: Phase 1

Answer 5

-Brief, partial repolarization
-90% of the fast Voltage-Gated Na+ channels opened during phase 0 close.
-10% of the Na+ channels remain open until repolarization is well underway. Then they finally close as well
-Another Voltage-Gated K+ channel ito1 Briefly opens
-Channel is only open over a limited range of voltage and time
K+ leaves the cell and repolarizes Em To ~ 0 mV, the plateau voltage of Phase 2

Question 6

Ventricular AP: Phase 2

Answer 6

• Plateau
• Near 0 mV the ito1 channel closes
• The iK1 channel continues to rectify
• This decreases the hyperpolarizing Effect of K+ and makes it easier for The cell to remain depolarized on The plateau
• While the iK1 channel is rectifying, a
• Voltage-gated Ca++ channel opens: slow or L-type Ca++ channel
  
  • similar to fast Na+ channel only it opens and closes much more slowly
  • When open, this channel increases the Ca++ permeability
  • Inward Ca++ current helps maintain the plateau voltage and initiates contraction in the ventricular cell

Question 7

Ventricular AP: Phase 3

Answer 7

• Repolarization
• During phase 2: remaining Ca++ channels close and iKr and iKs delayed K+ rectifying channels fully open
• The iK1 channel that was plugged in on depolarization is unplugged, Finishing repolarization
• Once back at the resting level, the iKr and iKs close and the membrane is ready for another action potential

Question 8

Differences in Nodal Action Potentials

Answer 8

• The duration of the nodal action potential is much longer
  
  • Phase 2, the plateau is absent in nodal potentials
• Phase 4, or resting potential is constant in the ventricular action potential.
• Phase 4 (pacemaker potential) in the nodal potential is NOT constant: depolarizes toward threshold.
  
  • All ion potentials are changing spontaneously
    
    • No stimulation or depolarization required
  • iK channel closes, decreasing hyperpolarizing K+ currents
    
    • Allows Na+ and Ca2+ to move in and depolarize
  • Na+ Funny channels: open rather than close on hyperpolarization
    
    • inward Na++ flow thru these channels depolarizes
  • Another voltage gated Ca2+ channel opens (iCaT)
    
    • Ca2+ completes the depolarization to threashold

Question 9

Parasympathetic Effects (Vagus)

Answer 9

• Vagal stimulation releases ACh to modify channel permeabilities
• Changes slow the heart rate
• Release of ACh
  
  • Depolarizes the threshold
  • During the pacemaker potential
    
    • Decreases Na+ permeability
    • Decreases Ca++ permeability
    • Increases K+ permeability
    • All of these permeability changes promote hyperpolarization causing it to take longer to reach threshold, thus slowing the heart rate

Question 10

Sympathetic Effects

Answer 10

• Sympathetic stimulation releases norepinephrine
• Norepinephrine ~ works opposite of ACh
• Release of norepinephrine during the pacemaker potential
  
  • Increases Na+ & Ca++ permeabilities
  • Decreases K+ permeability
• All of these permeability changes promote depolarization
• Allows membrane to reach threshold faster
  
  • Decreases time between action potentials
  • Increases heart rate