Action Potential 1

Question 1

Recognise the Different Phases of the AP

Answer 1

Phase 0 - Upstroke
Phase 1 - Early repolarisation (varied in cell types)
Phase 2 - Plateau
Phase 3 - Repolarisation
Phase 4 - Resting membrane potential (if present)

Question 2

Why different CMs have different AP shapes

Example of mid-myocardium

Answer 2

• Different series of ion channels expressed
• Different extent of certain channel expression

The mid-myocardium repolarises slower than epi-endocardium:

• Less transient outward current I(to)
• Half as much slow potassium I(Ks)

Question 3

The Voltage-gated Na current

Answer 3

• Responsible for the rapid upstroke in ventricular (and atrial but not SAN) myocytes
• The all-or-nothing AP
• Channels are primed by the resting membrane potential to open and cause massive influx of Na
• Inactivated at around 40mV

Question 4

Na channel inactivation and the refractory period

Answer 4

• Na channels must cycle through closed position (via repolarisation) in order to be re-activated once opened
• The cell must therefore wait to repolarise enough (absolute refractory period) before another depolarisation (AP) is possible
• Ball and chain inactivation:
  Ball inactivates open channel
  Ball removed when channel is closed

Question 5

Channel Nonmenclature

Answer 5

1. The ion
2. The main physiological regulator/gate
3. The gene family/subfamily
4. The specific isoform
   eg:

NaV1.5 (Na, voltage, gene 1, isoform 5)

Question 6

Early repolarisation and the role of I(to)

Answer 6

• The first notch of repolarisation after the upstroke
• Shortens the APD
• Highly pronounced in Purkinje fibres

I(to)

1. Ca-insensitive current (2 voltage sensitive K channels)
2. Ca-activated Cl channels
   - K out/Cl in both act to repolarise the membrane

Question 7

L-Type Ca Channel

Answer 7

• Opened at far more positive membrane potential
• These channels allow excitation-contraction coupling via Ca-induced Ca release
• Allows Ca into the cell, stay open during plateau to give SERCA time to refill the SR
• This Ca binds the ligand-operated RyR, causing SR Ca release

Question 8

Ca channel inactivation

Answer 8

• Ca from SR and Ca permeating the channel inactivate it

- Voltage also plays a role

Question 9

Inward Rectifier Current

Answer 9

• Ik1
• Unusual IV relationship, inactive in initial depolarisation
• Only activates between -40 to -80mV
• Responsible for the late repolarisation and regulates APD

Question 10

Delayed Rectifier Current

Answer 10

• IK(ur), IK(r)/HERG and IK(s)
• Slow activation coupled with slow inactivation of the outward currents produces the plateau
• No S4 V-sensing domain, rely on Mg and polyamide physiology to block the channels by sitting in the mouth

Question 11

Inward vs Outward Current

Answer 11

• Inward* = negative current
• Outward = positive current
• +ve ions IN or -ve out