0623 - The Cardiac Action Potential

Question 1

What are the cellular specialisations that support AP spread?

Answer 1

Cardiac myocytes, joined by intercalated disks form the bulk of the myocardium and give the heart its contractile force. Specialised ‘impulse conduction system’ cells form the SA and AV nodes, and the Purkinje fibres. These differ from myocytes due to different ion channels and amounts of contractile protein. Rounded cells are ‘pacemakers’, elongated cells are ‘conductors’.

Question 2

Identify the phases in the cardiac myocyte action potential. What is happening in each phase in terms of current and channels?

Answer 2

Question 3

Identify the phases in the cardiac ICS action potential. What is happening in each phase in terms of current and channels?

Answer 3

Phase 0 – I(Ca)L (L-type Calcium) spike, amplitude is [Ca] dependent. Minimal I(Na) involved as hyperpolarisation not reached.

Phase 3 – I(Ca) inactivated, I(K) (potassium) activated, causing repolarisation and slight hyperpolarisation.

Phase 4 – Deactivation of I(K), opening of slow Na (I(f)) – Funny Current/HCN channels, depolarise until Ca spike activates around -55mV. Mixed cation current, comprising of I(f), I(CaT). Funny current is activated/triggered by hyperpolarisation of RMP below ~-50-60

Question 4

What causes the myocyte refractory periods (Absolute, effective, and relative).

Answer 4

Absolute (ARP) – very few Na+ channels can be reactivated above Vm -50mV – ARP thus ends at -50mV. (Key difference with neurons, where Na channels inactivate until membrane hyperpolarises, then close and can re-activate). Effective (ERP) – Essentially the same as ARP, with a slightly lower threshold (around -60mV), during which time action potentials cannot spread from other cells, but could be initiated by that cell. Relative (RRP) – Commences immediately after ARP (-50mV), and continues to RMP (-90mV). During this time, any AP generated will have a smaller amplitude and slower rise.

Question 5

What determines the spread of an AP through cardiac tissue?

Answer 5

Slow compared to nervous tissue. Key factor – conductance of gap junctions (more and larger = faster). Also fibre diameter (large Purkinje fibres = faster, lower internal resistance). AV node delay is due to scarcity of gap junctions. Intracellular current spreads forward through gap junctions. Extracellular current spreads backward.

Question 6

Why is there a ‘hierarchy of pacemakers’ in the heart.

Answer 6

There are 3 areas with pacemaking cells – SAN (60-100 BPM), AVN (40-60 BPM), and Purkinje (20-40 BPM). The cells with the highest AP rate (SAN) set the pace of the heart, as they are capable of depolarising the cells with slower AP rates. Thus, the slower cells are subservient to, and have their pacemaker abilities inactivated by, the faster cells, provided the faster cells are functioning correctly.

Question 7

What is the difference between ventricular repolarisation and repolarisation in other areas of the heart?

Answer 7

In the ventricles, the last cells to depolarise (muscle cells), are the first to repolarise, with the Purkinje bundle branches having the longest AP. This prevents ventricular arrhythmia.

Question 8

Which drug is most valuable in inactivating the pacemaker potential?

Answer 8

Nifedipine can block the L=type Calcium channels, preventing the Ca spike and inactivating the pacemaker potential.

Question 9

Stricker SUmmary

Answer 9

• Gap junctions are instrumental in spreading APs.
• Cardiac myocyte and ICS have different ionic currents.
• AP in myocytes has 5 phases during which specific currents are activated/inactivated.
• AP propagation speeds up in larger fibres and when gap junction conductance is large.
• Refractory period is determined by extent of repolari- sation (re-activation of Na+ channels).
• Pacemaker current is largely carried by HCN channels with no NaV current.
• There is a 3-tiered hierarchy of pacemakers running at different frequencies: SAN > AVN > Purkinje fibres.
• A multitude of drugs is used that affect AP.