Action Potential 2

Question 1

The L-Type Ca Channel

Answer 1

• Ca influx during the upstroke and continues, prolonging the AP

Question 2

The L-Type Ca Channel

Answer 2

• Ca influx during the upstroke and continues, prolonging the AP
• Supports inward current during the plateau

Question 3

Maintaining the Plateau

Answer 3

• Slow generation of outward current against the slow inactivation of inward current

Question 4

K Currents and distribution in contractile CMs

Answer 4

Most activated by depolarisation to establish outward flow

• Ik(ur) mainly in atria
• Ik(r) and Ik(s) in atria and ventricles

Question 5

Voltage/Ca sensitive K channels Structure

Answer 5

• 6 TMDs combined from four monomers

- S4 voltage sensing segment

Question 6

Ik1 Structure

Answer 6

• 2TMDs

- One pore

Question 7

Delayed Rectifier Current

Answer 7

• K(ur) and K(s)

- Ik(r): coded for by HERG (human ether-a-go-go)

Question 8

Ik(r) Importance

Answer 8

• Channel = Kv11.1
• Slow, gentle activation important for controlled repolarisation
• Promiscuous drug binding
• Used for assessing cardiac safety of new drugs

Question 9

Ik1
- What’s unusual?

• What is the role in the AP?

Answer 9

The Inward Rectifier Current

• IV relationship (not activated by depolarisation) instead active between -40 to -80mV
• Large conductance causes rapid repolarisation after the plateau
• Main component of K flux at rest, maintains resting Em approaching equilibrium potential of K

Question 10

Ik1 voltage control

Answer 10

• No S4 voltage sensing unit
• Physiological effect of Mg and polyamines (spermine/spermidine)
• These sit in the channel mouth to block it at certain voltages

Question 11

NCX

Answer 11

• Stoichiometry = 3Na to 1Ca (therefore electrogenic)
• Exchanger that does not use ATP
• Tends to efflux Ca (against its CG) by allowing Na influx (along its CG)
• In the steady state it balances the influx of Ca through L-Type Ca channels

Question 12

ATP-sensitive K current

Answer 12

• Senses ATP:ADP
• ADP increases in hypoxia
• Decreases the APD
• Start of hypoxia-related arrhythmogenic processes

Question 13

ACh-Sensitive K current

Answer 13

• Prevalent in SAN and AVN

- Under influence of parasympathetic Nervous system

Question 14

Late Na Current

Answer 14

• May be different isoform than Nav1.5
• May be Nav1.5 channels behaving strangely
• Prolongs Na influx
• Markedly increased in HF

Question 15

Problems with late Na current

Answer 15

• APD prolonged (EADs)
• Increased [Na]i can reverse NCX
• Increased [Ca]i can potentiate DADs

Question 16

The Funny Current

Answer 16

• HCN4 (also 1 and 2) channels
  1. Activated on hyper-polarisation
  2. Not selective (allows Na or K) but mainly uses Na

Question 17

I(f) with ACh, Beta-ARA, Ca

Answer 17

ACh
- Increases Em-dependence

Beta-ARA
- Decreases Em-dependence (more probability of acting at a given/higher Em)

Ca
- Increases If

Question 18

PMC depolarisation

Answer 18

1. I(f) activates, then deactivates
2. T-Type Ca channels activate/deactivate
3. L-Type Ca channels activate (-40 to 0mV) and cause bulk of the upstroke

Question 19

PMC repolarisation

Answer 19

• Mainly Ik(r) and Ik(s)
• Little I(to) involvement
• No Ik1