Action Potential 2 Flashcards
The L-Type Ca Channel
- Ca influx during the upstroke and continues, prolonging the AP
The L-Type Ca Channel
- Ca influx during the upstroke and continues, prolonging the AP
- Supports inward current during the plateau
Maintaining the Plateau
- Slow generation of outward current against the slow inactivation of inward current
K Currents and distribution in contractile CMs
Most activated by depolarisation to establish outward flow
- Ik(ur) mainly in atria
- Ik(r) and Ik(s) in atria and ventricles
Voltage/Ca sensitive K channels Structure
- 6 TMDs combined from four monomers
- S4 voltage sensing segment
Ik1 Structure
- 2TMDs
- One pore
Delayed Rectifier Current
- K(ur) and K(s)
- Ik(r): coded for by HERG (human ether-a-go-go)
Ik(r) Importance
- Channel = Kv11.1
- Slow, gentle activation important for controlled repolarisation
- Promiscuous drug binding
- Used for assessing cardiac safety of new drugs
Ik1
- What’s unusual?
- What is the role in the AP?
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
Ik1 voltage control
- 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
NCX
- 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
ATP-sensitive K current
- Senses ATP:ADP
- ADP increases in hypoxia
- Decreases the APD
- Start of hypoxia-related arrhythmogenic processes
ACh-Sensitive K current
- Prevalent in SAN and AVN
- Under influence of parasympathetic Nervous system
Late Na Current
- May be different isoform than Nav1.5
- May be Nav1.5 channels behaving strangely
- Prolongs Na influx
- Markedly increased in HF
Problems with late Na current
- APD prolonged (EADs)
- Increased [Na]i can reverse NCX
- Increased [Ca]i can potentiate DADs
The Funny Current
- HCN4 (also 1 and 2) channels
1. Activated on hyper-polarisation
2. Not selective (allows Na or K) but mainly uses Na
I(f) with ACh, Beta-ARA, Ca
ACh
- Increases Em-dependence
Beta-ARA
- Decreases Em-dependence (more probability of acting at a given/higher Em)
Ca
- Increases If
PMC depolarisation
- I(f) activates, then deactivates
- T-Type Ca channels activate/deactivate
- L-Type Ca channels activate (-40 to 0mV) and cause bulk of the upstroke
PMC repolarisation
- Mainly Ik(r) and Ik(s)
- Little I(to) involvement
- No Ik1
