CVS - Electrical/Molecular Mechanisms In The Heart

Question 1

What is responsible for setting up the potassium gradient in a cardiac myocyte?

Answer 1

Movement of K+ ions out of the cell (down their concentration gradient)

Question 2

At which point does the net outflow of K+ from the myocyte stop?

Answer 2

When Ek is reached

Question 3

Why is the resting membrane potential of a cardiac myocyte not the same as Ek?

Answer 3

The cell has a very small permeability to other ion species at rest

Question 4

Why must cardiac myocytes be electrically active?

Answer 4

It allows them to fire action potentials, which trigger a rise in cytosolic [Ca2+], allowing actin and myosin interaction

Question 5

What causes the upstroke of the ventricular cardiac acton potential?

Answer 5

Opening of voltage-gated Na+ channels, leading to an influx of Na+

Question 6

What causes the initial repolarisation of the cardiac myocyte during action potential?

Answer 6

Transient voltage gated K+ channels

Question 7

What causes the plateau in the cardiac action potential?

Answer 7

Opening of voltage-gated Ca2+ channels causes an influx of Ca2+w high balances with K+ efflux

Question 8

What causes the repolarisation in the cardiac action potential?

Answer 8

Effluent of K+ through voltage gated K+ channels

Question 9

What are HCN channels?

Answer 9

“Hyperpolarisation-activated, cyclic nucleotide-gated” channels which allow influx of Na+ ions which depolarise the cells.

Question 10

Why is the SA node said to not have a proper resting membrane potential?

Answer 10

The cells are never properly at rest, as they spontaneously depolarise

Question 11

What is the ‘funny current’?

Answer 11

Otherwise known as the pacemaker potential, this is a mixed sodium-potassium current that activates upon hyperpolarisation at voltages below -50 mV

Question 12

What is responsible for the upstroke in SA node action potential?

Answer 12

Opening of V-gated Ca2+ channels

Question 13

What is responsible for the repolarisation of the SA node action potential?

Answer 13

Opening of voltage-gated K+ channels

Question 14

Why does the SA node set the rhythm of the heart?

Answer 14

It is the fastest to depolarise

Question 15

What is caused by action potentials firing too slowly?

Answer 15

Bradycardia

Question 16

What is caused by action potentials failing?

Answer 16

Asystole

Question 17

What is caused by action potentials firing too quickly?

Answer 17

Tachycardia

Question 18

What is caused by electrical activity in the heart becoming random?

Answer 18

Fibrillation

Question 19

What is the normal range of plasma K+ concentration?

Answer 19

3.5 to 5.5 mmol/L

Question 20

What is hyperkalaemia?

Answer 20

This is when the plasma K+ concentration is too high (over 5.5 mmol/L)

Question 21

What is hypokalaemia?

Answer 21

This occurs when plasma concentration is too low (less than 3.5 mmol/L)

Question 22

Why are cardiac myocytes so sensitive to changes in [K+]?

Answer 22

K+ permeability dominates the resting membrane potential, and the heart has many different kinds of K+ channels

Question 23

What is the effect of hyperkalaemia on the cardiac myocytes?

Answer 23

If plasma K+ is raised, Ek is less negative so the membrane depolarises a bit. This inactivates some of the voltage-gated Na+ channels and slows the upstroke.

Question 24

What is the main cardiac risk associated with hyperkalaemia?

Answer 24

The heart can go into asystole

Question 25

What are the treatments for hyperkalaemia?

Answer 25

• calcium gluconate
• insulin and glucose

These will not work if the heart has already stopped

Question 26

At what point is hyperkalaemia described as severe?

Answer 26

Above 6.5 mmol/L

Question 27

What is the effect of hypokalaemia?

Answer 27

Lengthens the action potential and delays repolarisation

Question 28

Why is hypokalaemia associated with ventricular fibrillation?

Answer 28

Longer action potentials can lead to ‘early after depolarisations’ (EADs) which lead to oscillations in the membrane potential. These can result in ventricular fibrillation.

Question 29

How is calcium released into cardiomyocytes?

Answer 29

Depolarisation opens L-type Ca2+ channels in T-tubule system. Localised Ca2+ entry opens CICR channels in the SR - these release 75% of calcium influx, while 25% enters across the sarcolemma

Question 30

How is the tone of blood vessels controlled?

Answer 30

Contraction and relaxation of vascular smooth muscle cells, located in tunica media and present in arteries, arterioles and veins

Question 31

What must be phosphorylated in order to enable actin-myosin interaction in vascular smooth muscle?

Answer 31

The regulatory myosin light chain

Question 32

What activates the contraction of vascular smooth muscle?

Answer 32

Noradrenaline activates a1 GPCR receptors

Question 33

How is contraction regulated in vascular smooth muscle?

Answer 33

• Ca2+ binds to calmodulin and activates Myosin Light Chain Kinase (MLCK)
• MLCK phosphorylates the myosin light chain to permit interaction with actin