Week 2

Question 1

The cardiac conduction system

Answer 1

1. Sinoatrial node: pacemaker
2. Electrical spread through atria
3. Atrioventricular node AVN delay
4. Conduction along his bundles and Purkinje fibres
5. Electrical spread from ventricular endocardium to epicardium

Question 2

Specific cardiac myocyte action potentials

Answer 2

SAN and AVN- spontaneous AP generation
Atrial and ventricular cardiac myocytes- no spontaneous firing
Purkinje fibres- very slow spontaneous AP generation

Differ from eachother in:
-shape/morphology
-underlying ionic basis

Question 3

The sinoatrial node: cardiac pacemaker

Answer 3

• in right atrium
  -80-100 APs/min
• no ‘resting’ membrane potential
• pacemaker potential, drifts up to the threshold so spontaneously generates APs

Question 4

Which ions are responsible for the pacemaker potential

Answer 4

1. Inward movement of Na+ (through HCN channels and not fast voltage gated channels)
2. Inward movement of Ca2+
3. Outward movement of K+ (but low conductance no IK1)

Overall: rate of Na+ and Ca2+ influx exceeds K+ efflux, membrane potential slowly rises towards threshold

Question 5

Which ions are responsible for the action potential

Answer 5

Fast inwards movement of Ca2+, rapid depolarisation phase (through voltage gated Ca2+ channels) . Up to ~10mv
Closing of Ca2+ channels
Outward movement of K+, repolarisation phase (through voltage gated K+ channels)

Question 6

SA node- autonomic control

Answer 6

Innervation of SAN:
- parasympathetic neurones carried in the Vagus nerve (CNX)- release ACh
- sympathetic neurones carried in thew cardiac sympathetic nerves- release noradrenaline NA

Intrinsic rate of the SAN is 80-100 action potentials/min but resting HR is 60-70bpm. ‘Vagal tone predominates’ and slows down

Question 7

SA node

Answer 7

-autonomic control of HR occurs by altering the slope of the pacemaker potential
-increased parasympathetic (vagal) activity decreases HR:
Vagal stimulation releases ACh which acts on M2 receptors expressed on SAN cells, increases K+ efflux (elevated K+ conductance), reduces slope of pacemaker potential so takes longer to get to threshold. Negative chronotopic effect
- increased sympathetic activity increases HR (cardiac sympathetic nerves):
Released noradrenaline acts on beta 1 receptors, increases Na+ and Ca2+ influx (increased Na+ and Ca2+ conductance), elevates slope of pacemaker potential so quicker to get ton threshold. Positive chronotopic effect
An increase in circulating adrenaline can act in the same way to increase HR

Question 8

The AV node

Answer 8

Only pathway from atria to ventricle is through AVN
Floor of right atrium
40-60APs/min
Electrical conduction is slowest through the AVN. AV delay ensures atrial depolarisation, contraction and ejection before ventricles depolarise. Slowest rate of conduction velocity
Takes longer to get to threshold, less steep pacemaker potential so fewer ap in a given time.

Question 9

The hierarchy of cardiac pacemakers

Answer 9

Sinoatrial node: 80-100 APs/min
Atrioventricular node: 40-60 APs/min
Purkinje fibres : 20-40 APs/min
HR will always be driven by the fastest pacemaker

Question 10

The ventricular cardiac myocyte

Answer 10

Stable resting potential -80–90mV
They do not spontaneously contract because of stable resting potential

Question 11

Phases of ventricular myocyte action potential

Answer 11

Phase 0- rapid depolarisation
Phase 1- partial rapid repolarisation
Phase 2- plateau
Phase 3- terminal repolarisation
Phase 4- stable resting potential

Question 12

Ventricular myocyte which ions are responsible for the action potential

Answer 12

Phase 0- inward Na+ movement (fast voltage gated Na+ channels)
Phase 1- inactivation of Na+ channels, activation of fast voltage gated K+ channels
Phase 2- inward Ca2+ movement and outward movement of K+ balanced
Phase 3- outward movement of K+ delayed rectifier K+ channels, new population of K+ channels, excess K+ movement out cell

Question 13

Refractory periods

Answer 13

Time from initial depolarisation of first AP to the point at which a second action potential can be stimulated
Absolute refractory period: no chance stimulating another AP up until phase 3
Relative refractory period: might be potential, terminal repolarisation phase 3 and 4
The refractory period is determined by the number of available and recovered (re-primed) voltage gated sodium channels

Question 14

Sodium channel recovery is time and voltage dependent

Answer 14

Sodium channels recover faster at more negative membrane potentials. The speed of return to “negative” RMP is controlled by the duration of the action potential APD
2 pulse protocol

Question 15

Gap junctions

Answer 15

Cardiac myocytes are electrically coupled due to the presence of gap junctions
Gap junctions: allow passage of positively charged ions between cardiac myocytes eg Na+ and Ca2+ if there is a charge gradient

Question 16

Conduction velocity

Answer 16

Both cells at negative resting membrane potential RMP, no charge gradient so no movement of positive ions
But if Na+ influx into cell 1 during depolarisation phase causes membrane potential to become more positive large change in gradient between cells so movement of positive ions into cell 2 via gap junctions
The movement of positive ions cause cell 2 to be more positive when it reaches threshold enough voltage gated Na+ channels open and AP triggered in cell 2
The overall conduction velocity is determined by the charge gradient between cells
This is set by the magnitude of depolarising current i.e the action potential amplitude APA
This can vary in disease leading to arrhythmia
CV can also be modified by gap junction expression/function