2.01 - The Cardiac Action Potential

Question 1

What are the cardiac specialisation supporting action potential spread?

Answer 1

Intercalated Discs and the Impulse conduction system

Question 2

What two structures form the intercalated disc? And describe them

Answer 2

Desmosomes: complexes of cell adhesion protein

Gap Junctions: made up from connexins. Form the electrical syncytium. Change in potential in one cell will spread throughout the myocardium

Question 3

What are the components of the impulse conduction system?

Answer 3

Sinoatrial node (SA)

Atrioventricular Node (AV)

Bundle Of His

Purkinje Fibres

Question 4

What is the resting membrane potential of a ventricular myocyte?

Answer 4

-90mV

Question 5

What are the phases of a ventricular myocyte action potential? Draw it…

Answer 5

0. Fast Depolarisation
1. Early (partial) repolarisation (fast)
2. Plateau
3. Final repolarisation (slow)
4. Restoration of RMP

Question 6

Describe Phase 0

Answer 6

Threshold at -60 to -70mV

Activation of fast inward (I_Na) channels.

Suppression of Inward (I_K1) channels

Overshoot determined by [Na⁺]

Question 7

Describe Phase 1 of the ventricular myocyte action potential

Answer 7

Early (partial) depolarisation

Inactivation of fast inward sodium channels (I_Na)

Activation of outward K channels

Question 8

Describe phase 2 of the ventricular myocytes action potential

Answer 8

Plateau (Ca²⁺ shoulder)

Activation of calcium channels –> influx of calcium

Question 9

Describe phase 3 of the ventricular myocyte action potential

Answer 9

Inactivation of inward calcium channels

Activation of outward potassium channel known as delayed rectifier

Reactivation of inward sodium and calcium channel

Question 10

Describe phase 4 of the cardiac myocyte action potential

Answer 10

Activation of fast inward potassium channel known as the inward rectifier

This determines resting membrane potential

Question 11

What are and describe the refractory periods in ventricular myocytes?

Answer 11

Aboslute Refractory Period: very few sodium channle can be reactivated above Vm_>-50mV

Absolute refractory period (ERP): only after this, myocytes nearby can be activated as current spread is too small for activation

Relative refractory period (RRP): Follow ARP, during this time no full AP can be generated

Question 12

Describe the speed of action potential propagation in the heart

Answer 12

Depolarisation spreads passively through the myoctes but is sped up by gap junctions between cells (the larger the junciton the faster)

Question 13

Which part of the conduction system of the heart is fastest?

Answer 13

Purkinje fibres. 4m/s

Compared to myocytes (1m/s), SAN (0.05m/s)

Question 14

What are the phases of an action potential in sinoatrial and atrioventricular nodes?

Draw it

Answer 14

0: Depolarisation
3: Repolarisation
4: Variable resting membrane potential

Question 15

Describe phase 0 of the nodal action potential

Answer 15

Mostly a calcium spike. Not much sodium involved

Activation of L-type Calcium channels

Question 16

Describe phase 3 of a nodal action potential

Answer 16

Inactivation of L-type calcium channels

Activation of delayed rectifier K channel

Question 17

Describe phase 4 of the nodal action potential

Answer 17

early deactivation of the delayed rectifier (turning off an outward is seen as a net inward current)

Followed by a set of opening of channels that generate an inward current - predominantly sodium

Question 18

Describe the pacemaker currents in nodal membrane potentials

Answer 18

The pacemaker potential of a nodal cell is due to the decay of the resting membrane potential until a calcium spike

It arises from a number of channels. Particularly I_f (funny) channel. This channel results in a mixed cation current but largely an inward sodium current leading to gradual loss of resting membrane potential and therefore depolarisation

Coded for by HCN genes (HCN4 in humans)

Question 19

Describe the hierarchy of the pacemaker cells

Answer 19

SA node: 60-100bpm. natural rate around 100bpm, but this is reduced due to parasympathetic activation

AV Node: 40-60bpm. Slower due to a smaller I_f current –> slower depolarisation –> decreasred heart rate. Will take over pacing if not paced in time by SA node. Decay rate not as steep as AVN –> longer to reach threshold –> rate drops

Purkinje cells: 20-40bpm. Even slower I_f than AV node plus the RMP is much more hyperpolarised (-90mV)

Cells with the highest AP rate set the heart rate as all other conduction system cells are depolarised by them and therefore rendered functionally inactive

Question 20

Describe the spread of excitation in the heart and the timing of excitation in the various parts of the heart

Answer 20

Atria are excited within 80-90ms (right before the left

The first excitation of the septum seen after a 140ms delay (AV delay)

Ventricles then excitied within 50-60ms with the right slightly earlier than the left

Ventricles excite faster than atria because there are larger fibres generating larger currents –> faster depolarisation

Question 21

List some pharmacological agents that are used to modify the cardiac action potential and the channels that they target

Answer 21