CARDIAC UNIT: INITIATION OF THE CARDIAC ACTION POTENTIAL

Question 1

Discuss the propagation of cardiac action potentials across cells

Answer 1

Depolarization is caused by sodium brought into the cell which activates more sodium channels. Current flows through gap junctions which depolarizes nearby cell

Ionic currents on cell surface → sodium channels open → intracellular current is created → voltage flows through gap junctions

Question 2

Determinants of action potential propagation:

Answer 2

• Difference in voltage between cells
• Resistance between cells (dictated by gap junctions)
• Threshold for AP firing
• Size of the cells
• Expression level of voltage-gated Na channels

Question 3

Give the function of sinoatrial node

Answer 3

controlled by the autonomic nervous system. Specialized cell that are more spindley in shape. Initiate action potentials

Question 4

Describe and give the function of pacemaker channel

Answer 4

• non-selective cation channel with structure similar to a K+- channel.
• Gated by cAMP. Allow sodium and potassium through.
• Hyperpolarization-activated cyclic nucleotide gated channel

Question 5

Heart electrical conduction pathway

Answer 5

Sinoatrial node → atrioventricular node → bundle of His → purkinje fibres

Question 6

Draw an SA node action potential, and compare it qualitatively with a cardiomyocyte action potential

Answer 6

Compared to other action potentials, SA node action potentials have:

Slower upstroke velocity (1)
SA nodes lack sodium channels and are instead depolarized by ICa. Calcium channels are slower to open than sodium channels

Reduced plateau duration (2)
ICa are inactivated after upstroke

Diastolic depolorization phase (3) Due to pacemaking HCN channel

Higher “resting” potential (4) Lack IK1 - important for resting membrane potential

Question 7

Describe the structure of HCN channels and how it is activated. Also, explain what ions can pass through HCN channels

Answer 7

• 4 alpha subunits each with 6 transmembrane proteins
• Gated by cAMP
• hyperpolarization (getting more negative) activates them
• cation selective; allows sodium into cells and/or potassium out of the cell
• normally, sodium wants to come into the cell to depolarize the membrane. the driving force of sodium is larger than potassium’s driving force as the cell is far from its equilibrium potential.

Question 8

Explain how the pacemaker (HCN) channel can be regulated by sympathetic input

Answer 8

• When the sympathetic nervous system is activated (often referred to as the “fight or flight” response), it releases the neurotransmitter norepinephrine onto the SA node.
• Norepinephrine binds to beta-adrenergic receptors on the surface of SA node cells.
• Activation of these receptors leads to the activation of adenylyl cyclase, an enzyme that produces cyclic adenosine monophosphate (cAMP) from ATP.
• cAMP binds to HCN promoting its activation.
• Increased sodium influx and potassium efflux through the HCN channels cause the cell to depolarize more quickly, increasing the heart rate.
• This sympathetic stimulation thus increases the rate at which the SA node generates electrical impulses, resulting in a faster heart rate.

Question 9

Explain how the pacemaker (HCN) channel can be regulated by parasympathetic input

Answer 9

• When the parasympathetic nervous system is activated (often referred to as the “rest and digest” response), it releases the neurotransmitter acetylcholine onto the SA node.
• Acetylcholine binds to muscarinic receptors on the SA node cells.
• Activation of these receptors inhibits adenylyl cyclase, reducing cAMP levels.
• Lower cAMP levels mean less activation at HCN channel, voltage dependency shifts to other direction (left shifted)
• HCN channels are now less permeable to sodium ions, less likely to pass an inward current. SA node depolarizes more slowly leading to slower heart rate.

Question 10

When you stimulate the vagal nerve, what happens?

Answer 10

decrease in heart rate

Question 11

What is the function of the AV node?

Answer 11

Gate keeper of electrical impulse generated by SA node;

The AV node slows down the electrical impulse generated by the sinoatrial node (SA node), which is the heart’s natural pacemaker. This delay allows the atria to contract and push blood into the ventricles before the ventricles contract. This delay is essential for proper coordination between the atria and ventricles during each heartbeat.

Question 12

What specialized features of the AV node allow it to slow down the electrical impulse generated by the SA node?

Answer 12

• Smaller cells and less ion channels → slower conduction velocity
• Fewer gap junctions → slower conduction velocity
• Slower intrinsic diastolic depolarization rate
• More negative Em → slower conduction velocity

Question 13

Define: Wolff-Parkinson-White (WPW) syndrome

Answer 13

an accessory atrioventricular pathway between the heart’s upper and lower chambers causes a fast heartbeat (tachycardia).

WPW syndrome is a heart condition present at birth (congenital heart defect).

Question 14

Describe conduction speed through the heart and explain why this conduction system is efficient

Answer 14

A: atrioventricular node → bundle of His (130ms)
B: bundle of His → apex (30ms)
C: endocardium → epicardium (30ms)

Question 15

Give the conduction velocity in m/s for:
- atria
- atrioventricular node
- bundle of His
- purkinje fibres
- ventricular muscle

Answer 15

• Atria: 1 m/sec
• Atrioventricular node: 0.05 m/s
• Bundle of His: 1 m/s
• Purkinje fibres: 4 m/s
• Ventricular muscle: 1 m/s

Question 16

Why do purkinje fibres conduct AP so fast?

Answer 16

Conduct action potentials quickly as they have a wide diameter (resulting in low resistance) and large number of gap junctions (also resulting in low resistance)