S1: Control of Cardiac Muscle

Question 1

How is the heart myogenic?

Answer 1

The heart generates electrical activity and contraction without the need for nerves (making it different to skeletal muscle)

Question 2

How does the heart produce electrical activity and lead to contraction?

Answer 2

It is based on two action potentials.
A pacemaker potential at the SAN controls heart rate. The impulse will travel through the heart which will cause an atria/ventricular potential in the cardiac muscle controlling contractility.

Question 3

What system modulates both heart rate and contractility?

Answer 3

The ANS

Question 4

Where does the initiation of heart beat occur?

Answer 4

SAN

Question 5

What is the SAN?

Where is it found and what is it’s function?

Answer 5

Sino Atrial Node is a small group of specialised cells located in the wall of the right atrium.

• It generates APs with rhythmical pacemaker activity in the absence of any nerve stimulation.
• These cells are independent from the rest of the cells

Question 6

Are SAN cells contractile?

Answer 6

No

They are primarily involved in the initiated of the electrical potential.

Question 7

What is the firing rate of APs at SAN?

Answer 7

Usually 1 per second

equalling heart rate (resting 60-80bpm)

Question 8

What innervates the SAN?

Answer 8

Sympathetic and Parasympathetic nerves

Question 9

What happens once the AP at the SAN has been generated?

Answer 9

It spreads through the atria to the AVN (atriventricular node) where it will be slowed down. It will then move down the bundle of His and finally the purkinje fibres which cause contraction.

Question 10

Why do SA node cells continuously generate APs?

Answer 10

SAN cells have an unstable/non-equilibrium resting membrane potential (RMP)
- It is higher that normal at -60mV (slightly more depolarised)

Question 11

Why do SAN cells have a RMP higher than normal?

Answer 11

This is because of the If channel (‘funny current’)
This is an Na+ ion channel activated by hyperpolarisation (unlike normal Na+ channels e.g. VGNC which are activated by depolarisation)

The more negative (repolarised) the membrane, the more the If channels will open and therefore Na+ will depolarise in causing it to depolarise.
This is why SAN cell membranes cannot reach normal RMP of -70/80mV as it can’t fully polarise fully due to these If channels.

Question 12

What are the three phases in the generation of pacemaker potentials at the SAN?

Answer 12

PHASE 4: The unstable resting membrane potential.
The ion channel is activated by hyperpolarisation and the If ion channels are open.
Sodium influx into the cell down its gradient prevents the RMP from reaching normal levels.

Near the end of this phase, the membrane starts to get more positive by depolarisation.

PHASE 0: Voltage gates calcium channels open and calcium starts to influx into the cell. More depolarisation occurs.

PHASE 3: The cell needs to repolarise. Activation of voltage gated potassium channels and K+ diffuses out of cell causing repolarisation to occur as the inside of the cell becomes more negative.

Question 13

What channels do you modulate if you want to modulate heart rate?

Answer 13

If channels

Question 14

What are resistant pathways between myocytes called?

Answer 14

Intercalated discs (gap junctions)

Question 15

What is the role of intercalated discs?

Answer 15

They facilitate conduction through the heart as they are low resistance pathways.
- They allow atria to conduct at the same time because it is very quick

Question 16

What is the role of the AVN?

Answer 16

It is an insulated area which slows conduction rate and allows filling of the ventiricles before cotnraction (allows atria to completely empty).
The AVN then transmits electrical activity to the fast conducting pathway of the bundle of His.

Question 17

Describe the resting membrane potential of AVN cells

Answer 17

Stable

Question 18

What stimulates the AP from AVN cells?

Answer 18

AP from the SAN

Question 19

What are the five phases in the generation of action potentials at the AVN?

Answer 19

PHASE 4: AVN cells are at resting potential around -90mV. They are waiting to be stimulated by electrical activity from the SAN.

PHASE 0: Upon stimulation, voltage gated Na+ channels are open and Na+ influxes in very quickly. causing an steep upstroke of depolarisation past threshold.

PHASE 1: This is the peak of the AP and the repolarising phase.

PHASE 2: This is the plateau phase. It is caused by the opening of VGCCs, where calcium influxes in but much SLOWER and channels are open for longer —> sustained Ca2+ influx that maintains the depolarisation (sustained depolarisation)

PHASE 3: VGCCs begin to close and VGKC will open allow K+ efflux causing membrane to become more negative and repolarisation starts to occur

Phase 4 process starts again

Question 20

How long does the plateau phase of AP at AVN last?

Answer 20

200-400ms

Question 21

Why is the plateau phase (sustained depolarisation) important?

Answer 21

During this period, myocytes are unexcitable (refractive). They cannot fire any more AP which means that there is no twitching.
Only one AP= One contraction (on ejection)
This is essential for proper ejection of blood from the heart.

Question 22

What is ventricular fibrillation?

Answer 22

There is lots of AP firing which doesn’t allow the ventricles to fill properly, so there is less cardiac output and less perfusion of organs

Question 23

How do AP produced by AVN cause contraction?

Answer 23

Contraction is caused by an increase in cytosolic Ca2+ levels during the plateau phase.
The higher the concentration of Ca2+, the further increase in the force of contraction.

Question 24

What are the 2 things that occur when Ca2+ influx occurs during the plateau phase?

Answer 24

1. The Ca2+ will directly bind with troponin causing conformational change displacing tropomyosin and allowing contraction.
2. Ca2+ acts as an ligand and will wind to the ryanodine receptor (RyR) on the SR causing calcium induced calcium release. These Ca2+ will also bind to tropomyosin.

Question 25

What effect on the heart does sympathetic nerves have?

Answer 25

Heart Rate: Chronotrophic effect

Force of Contraction: Ionotrophic effect

Question 26

Where from the spinal cord does sympathetic nerves come from that innervates both SAN and atria/ventricles?

Answer 26

T1-T5

Question 27

What do the sympathetic nerves release and what receptor does the chemical act on?

Answer 27

They release noradranaline that act at B1-adrenoreceptors on SAN and cardiac myocytes.

Question 28

Explain what happens when B1 receptors are activated at the SAN

Answer 28

There is an increase in pacemaker frequency causing an increase in heart rate (tachucardia).

This is because there is an increase of If receptors activated which causes more membrane unstability so more AP firing.

Question 29

Explain what happens when B1 receptors are activated at the ventricles

Answer 29

It cause calcium channels to be open for longer, causing an greater influx of Ca2+ leading to higher levels in the cell. This increases the force of contraction.

Question 30

Which Ga mediated pathway do B1 adrenoreceptors take?

Answer 30

Gas coupled
Positively associated with adenylate cyclase, hence cAMP is increased and more PKA activated which phosphorylates Ca2+ channels and also phosphorylates K+ channels leading it to hyperpolarise quicker so contraction is briefer

Question 31

What effect on the heart does parasympathetic nerves have?

Answer 31

Heart rate: Chronotropic effect

Parasympathetic system has a chronotropic effect only

Question 32

What do the parasympathetic nerves release and what receptor does the chemical act on?

Answer 32

They release acetyl choline which act at muscarinic (M2) receptors on SAN cells

Question 33

Name the parasympathetic nerve innervating the SAN

Answer 33

Vagus from brain stem

Question 34

Explain what happens when M2 receptors are activated at the SAN

Answer 34

Calcium channels are less open causing a decrease in pacemaker frequency resulting in a decrease in heart rate (bradycardia)

Question 35

Which Ga mediated pathway do M2 take?

Answer 35

M2 receptors are GI coupled.
They are negatively associated with adenylate cyclase so have the opposite effect as less cAMP is produced and there is less activated PKA