Cardiac action potential

Question 1

Myocardium phase 0

Answer 1

1. Fast, voltage-gated Na+ channels open. The membrane permeability to Na+ becomes much greater than the membrane permeability to K+. Na+ ions enter the muscle cell.
2. The membrane potential rises swiftly towards ENa due to inward Na+ current (INa), but ENa is never reached because…
3. K+ channels carrying the transient outward current (Ito) begin to open at the end of Phase 0, as the Na+ channels inactivate NB. Decrease conduction speed by prolonging Phase 0
   Phase 0 gives rise to the QRS complex in an ECG

Question 2

Myocardium phase 1

Answer 2

1. Na+ channels are inactivated
2. K+ channels carrying the transient outward current (Ito) are all open by now, allowing K+ to leave the cell. These are special K+ channels that open and inactivate quickly.
3. Ito partially repolarizes the membrane (by about 10mV)
4. During this phase, the slower Ca2+ channels begin to open as well. However since they are slow to open, their effect is not seen until phase 2

Question 3

Myocardium phase 2

Answer 3

early plateau:

1. Ca2+ channels continue to open, allowing Ca2+ to enter the cell.
2. K+ channels that produce Ito are still open, allowing K+ to leave the cell.

late plateau

1. Ca2+ channels are all open by now and the membrane permeability to Ca2+ is high. Ca2+ rushes into the cell, producing the slow inwards current Isi or ICa. This opens the RyR2 receptors (see CV week 2) causing the muscle cell to contract.
2. By this time, the K+ channels that produce Ito have become inactive
3. The membrane potential rises towards ECa due to inward Ca2+ current, but ECa is never reached because…
4. The delayed rectifier K+ channels begin to open, producing IK, which opposes ICa

Question 4

Myocardium phase 3

Answer 4

1. ICa channels inactivate
2. The membrane potential rapidly returns to baseline as IK becomes fully active
3. The inward rectifier opens during the latter part of phase 3. It conducts an outward current, IKir or IK1 and completes repolarization. These are special K+ channels that open as the membrane potential gets more negative, and are the reason that the RMP of myocardial cells is so close to EK¬. This low RMP ensures that more of the Na+ channels are closed, hence more are available to open in Phase 0, allowing for a faster depolarization.
4. Late in phase 3, all of the inactivated channels begin to close: INa, Ito and ICa channels

Question 5

Myocardium phase 4

Answer 5

1. The IKir channels are fully open and clamp the RMP close to EK.
2. The remaining inactivated channels close

Question 6

Purkinje cell AP

Answer 6

same for the working myocardium, except they also express the funny current (If), so phase 4 has a slower, upward sloping depolarization

Question 7

Pacemaker cell AP

Answer 7

no active Na and no RMP, constant state of partial depolarization

Question 8

Pacemaker cell phase 0

Answer 8

1. Ca2+ channels open, producing the slow inwards current Isi or ICa. Since ICa is slower than INa, the rate of rise of the AP is slower
2. The membrane permeability to Ca2+ is high, and the membrane potential rises towards ECa due to inward Ca2+ current, but ECa is never reached because…
3. The delayed rectifier K+ channels begin to open, producing IK, which opposes ICa
4. ¬As the IK channels open, the ICa channels begin to inactivate

Question 9

Pacemaker cell phase 3

Answer 9

1. Ca2+ channels inactivate
2. IK repolarizes the membrane
3. The funny current, If , activates. The funny currents in an inward positive current that carries both K+ and Na+ (but Na+ more readily) and opposes the repolarization. Like IKir, it becomes more active as the membrane potential gets more negative.

Question 10

Pacemaker cell phase 4

Answer 10

“diastolic depolarization”
1. The delayed rectifier current (IK) is open during this phase, but closes with time
2. As the delayed rectifier channels close, If depolarizes the membrane until threshold potential is reached at which point the Ca2+ channels open.
NB. Shorten phase 4 to increase heart rate.

Question 11

Absolute refractory period

Answer 11

cannot initiate another AP because Na channels are inactive

Question 12

Relative refractory period

Answer 12

as the MP becomes more negative, more Na channels have switched from inactive to closed –> more available to open –> AP happens faster

Question 13

Conduction velocity factors

Answer 13

Size of cells: smaller = greater resistance
# gap junctions: more gaps = faster velocity
Rate of rise of AP: faster rise = faster velocity

Question 14

Conduction velocity among pacemaker cells

Answer 14

Purkinje>Bundle of His> ventricle/atria> SA and AV nodes

Question 15

Intrinsic firing rates

Answer 15

SA: 60-100
AV and bundle of His: 50-60
Purkinje: 30-40

Question 16

Cardiac skeleton

Answer 16

a band of fibrous tissue at the base o the atria that prevents electrical conduction from the atria to the ventricles (the only pathway through is the Bundle of His).