Lecture 3 - Cardiac Electrical Activity

Question 1

Why does the SA node generate APs spontaneosly?

Answer 1

Because the RMP of the SA nodal cells are spontaneous

Question 2

What are the 3 phases of of a SA nodal cell repolaristion?

Answer 2

0, 3 and 4.

• Phase 4: Pre-potential or pacemaker potential
• Phase O: Upstroke
• Phase 3: Repolarisation

Question 3

Describe what occurs in phase 4

Answer 3

This is the pre-potential/ pacemaker potential

• The initial potential of an SA node is ~-60mV to -70mV and it declines sponteneously (becomes less negative, so it moves up the page)
• The slowly declining potential is called the pre-potential or pacemaker potential
• The spontaneous decline is caused by funny sodium channels, these are funny because they open with polarisation (when it becomes more -ve, whereas skeletal muscle Na+ channels open with depolarisation). The inward current of Na+ is denoted as i_f since the influx is caused by funny sodium channels.

Question 4

What are the two factors which cause the decay of the pacemaker potential?

Answer 4

1. Firstly it’s caued by a special pacemaker current, which is an inward Na+ current. This inward Na+ current (i_f) progressively depolarises the cell.
2. The second factor is the decreasing membrane permeability to K+ (G_K) with depolarisation of the membrane. As a result, as it gets more negative the outward current of K+ (i_K) falls progressively (which makes the cell more +ve) allowing the inward Na+ current (i_f) to dominate more and more.

Question 5

What happens during phase 4?

Answer 5

This is the pre-potential/ pacemaker potential.

The slowly declining potential is called the pre-potential. The pacemaker potential is due to

• The funny current (i_f) - inward Na+ current
• And the declining K+ permeability (decreasing outward K+ current)

Question 6

What happens when the membrane potential reaches about -50mV to -40mV?

Answer 6

Voltage operated calcium channels begin to open and a small inward current of Ca2+ (i_CaT) contributes to the final third of the pacemaker potential and triggers the action potential.

So the spontaneous declines in the membrane potential due to the funny sodium channels and lowered conductance of K+ only have to reach -50mV and -40m before Ca2+ channels open to cause depolarisation - these are T- type channels (trigger channels)

Question 7

What happens in phase 0 for nodal cells?

Answer 7

• The upstroke of the AP in the SA node is slow rising because the cells of the SA node (and AV node) lack functional fast sodium channels
• The “0 phase” of the action potential is due primarily to the slow inward current of Ca ions (i_Ca) (increased G_{Ca (Ca conductance)})
• After the T-type channels are opening the Ca L channels open to give the up shoot in action potential
• The progressive depolarisation is opposed by outward K+ current, i_k

Question 8

What happens during phase 3: Late repolarisation

Answer 8

During repolarisation the K+ channels open to cause and outward current of K+, which makes the membrane potential more negative.

The repolarisation makes the potential return to negative conditions, and this then allows the funny sodium channels to open again. So essentially one action potential turns on the next one. There is no pause between the action potentials, as this allows for continous beating, because if there was a pause there would have to be something to start it again

Question 9

Describe the autonomic control of the heart rate

Answer 9

The heart rate is controlled by the frequency of APs in the SA node, which normally discharges 100 times/min.

The autonomic input controls the rate of discharge.

The SA node is innervated by

• Vagus nerve (PNS fibres)
• Cardiac nerves(SNS nerve fibres
• Parasympathetic stimulation reduces heart rate (HR)*
• Sympathetic stimulation increases heart rate (HR)*

Question 10

What happens when there’s sympathetic stimulation of the SA node?

Answer 10

The HR increases, since the slope of the pacemaker potential increases, and the spontaneous rate of the SA node depolarisation is increased - which causes an increased heart rate.

This happens because Noradrenaline is released from the symapthetic nerve endings, and this binds to a B₁-adrenergic receptors.

This causes Sodium (G_Na) and Caclium conductances (Gca) are increased and inward calcium (ica) aand sodium currents (i_f) are increased.

This makes the slope of the pacemaker potential increase.

Question 11

Describe intracellulary how NA increases Ca2+ and Na+ conductance

Answer 11

Na binds to B1-adrenergic receptor. Binding of the NA leads to a rise in the intracellular conc of cAMP. The cAMP increases the i_f (inward Na+ current).

cAMP activates protein kinase A which phosphorylates the Ca channel and thereby increases i_ca (inward Ca2+ current).

Question 12

Besides phosphorylating the Ca channel to increase inward Ca2+ current, what else does protein kinase A do?

Answer 12

Protein kinase A also phosphorylates the K channel involved in repolarisation

• This increases the repolarising K+ current (ik)
• This shortens the duration of the action potential, since it repolarises quicker.
• Without this effect the long duration of the cardiac action potential would begin to limit heart rate

Question 13

How does PNS stimulation affect the heart rate?

Answer 13

PNS stimulation of the SA node reduces the slope of the pacemaker potential and hyperpolarises the SA node, therefore it takes longer to get to threshold, and since it takes longer it slows the HR.

This is done by Ach binding to it’s muscarinic (M₂) receptor. The binding of Ach leads to a fall in the intracellular concentration of cAMP. This reduces the effects of symapthetic stimulation (it reduces i_ca and i_f) - this results in a reduced slope of the pacemaker potential.

Question 14

How does the PNS cause hyperpolarisation?

Answer 14

Ach binds to M₂, and this activates Ach-sensitive potassium channel (K_ACh). The activation of Ach-sensitive potassium channels increased the potassium conductance (G_K), and so more K+ leaves the cell - making it more negative and hyperpolarised.

The more negative the membrane potential, the lower the likelihood of funny sodium channels opening. And it reduces the efficiency of the the channels due to reduced cAMP, so the slope of the pacemaker potential is decreased.

Question 15

What does the PNS reduce the intrinsic SA node pulse to?

Answer 15

Natural SA rate is ~100bpm, at rest PSNS reduces rate to ~70bpm - this is called vagal tone.

Increased PSNS causes bradycardia, and decreased PSNS and increased SNS causes tachycardia

Question 16

Whats the instrinsic rates for the AV node and purkinje fibres?

Answer 16

• AV node: 40-50 bpm
• Purkinje fibres: 20-30 bpm

if the conducting pathway doesn’t work, then the AV node or purkinje fibres should kick in and provide an “escape rhythm”.

The fast rate of the SA node supresses the pacemaker cells of the AV node and purkinje fibres

Question 17

What does the excitation-conduction system of the heart consist of?

Answer 17

• The SA node
• The AV node
• The bundle of His
• The left and right bundle branches
• The purkinje fibres

to get to the ventricles the AP has to pass through the atrioventricular ring.

Question 18

The cardiac muscles are joint together intercalated disks (which consists of gap junctions and desmosomes) to form a:

Answer 18

Electrical syncytium.

The gap junctions allow for continuous connection of cells so the impulse moves from cell to cell.

It allows for conduction of excitation.

Question 19

A stimulus arising at any point in the ventricle leads to what?

Answer 19

The complete contraction of both chambers (all-or-none contraction)

The gap junctions permit cell-to-cell conduction of excitation hence the myocardial cells form a functional syncytium

Question 20

What is the velocity of the AP through the heart?

Answer 20

AP conducted through the atrial muscle at ~0.5 ms-1, then is slowed through the AV node to ~0.05 ms-1. After the delay at the AV node, it then moves through the myocardium at 0.5ms-1.

The AV node provides a delay which permits full depolarisation and contraction of the atria before the ventricles are depolarised.

This allows for a fairly synchronous depolarisation of all regions of the ventricles. The conducting cells are modified cardiac muscle cells called purkinje fibres.

Question 21

What are the 5 stages for the ventricular muscle cell action potential?

Answer 21

• Phase 4: Resting membrane potential
• Phase 0: Upstroke
• Phase 1: Early repolarisation
• Phase 2: Plateau phase
• Phase 3: Late repolarisation.

Question 22

Describe phase 4 of the ventricular muscle cell action potential

Answer 22

This is the resting membrane potential, and is mainted by i_k and i_b (background current)

At rest the membrane potential is held around -80mV

Question 23

Describe phae 0 upstroke

Answer 23

The adjacent cell draws charge from the resting membrane potential, and reaches a threshold of -65mV, the membranes ionic permeability changes and the cell rapidly depolarises and overshoots to a potential of +40 mV.

The sharp depolarisation is due to a rapid increase in the permeability to Na+ ions.

At the threshold potential votlage sensitive Na+ channels (Fast channels) open, and increase the sodium conductance 100 times (this is why it’s so fast). Rapid flux of Na+ ions into the cell (i_Na) , the membrane potential doesn’t reach E_Na because the outward K current is still flowing.

Question 24

What happens during phase 1 during ventricular muscle cell action potential

Answer 24

Phase 1 is early repolarisation. There is a brief overshoot because the fast Na+ channels are self inactivating - this leads to a decrease in inwards Na current (Sodium conductance G_Na)

Within a couple of milliseconds the membrane voltage repolarises a few mV, owing to an outward current of K+ ions (i_to)

Question 25

What happens during phase 2 of a ventricular muscle cell action potential?

Answer 25

Phase 2 is the plateau phase, where the repolarisation plateaus.

• Cardiac muscles display a unique feature called the plateau
• This is a sustained depolarisation.
• There is a small but sustained inward current of Ca2+ ions down their electrochemical gradient - due to the opening of Ca2+ channels.
• Voltage operated Ca channels, which begin to operate when the cells depolarises to -30mV to -35mV (during rapid depolarisation)
• The inward Ca+ current is almost sufficient to counterbalance the outward K+ current.
• i_Ca almost stabilizes the potential at 0 mV to -20mV
• In the later part of the plateau phase, calcium channels are beginning to inactivate
  
  • The inward current during this stage is due partly to Na ions passing in through the Na-Ca exchanger (Na-Ca exchanger)

Question 26

What happens in phase 3 in ventricular muscle cell action potentials

Answer 26

Phase 3 is Late repolarisation.

• The potassium conductance (G_K) increases towards the end of the plateau phase as the calcium channels inactivate
• K+ leaves the cell generating a K+ current (i_K)
• This produces a repolarisation towards resting potential.

Question 27

Describe to yourself what channels open during each stage of the ventricular muscle cell action potential

Question 28

Why can’t cardiac contracile force summate, and produce tetanic contractions?

Answer 28

Since the electrical and mechanical activity overlap considerably in time

This causes the refractory periods overalp competely with the muscle contraction, and since the Na+ channels are inactivated during this period no other contractions can be generated. The Na+ channels remain inactive until the membrane returns to a ptoential below -20mV.

From the AP upstoke, during the subsequent plateau and until repolarisation reaches about -20mV, cardiac myocytes are inexcitable - this is the absolute refractory preiod (lasts ~250ms in an AP that lasts about 300ms.