Electrical and molecular mechanisms in heart and vasculature

Question 1

Describe the functioning of cardia myocytes

Answer 1

Cardiac myocytes can spontaneously depolarise, firing an action potential which triggeres an increase in cytosolic Ca²⁺

Rise in Ca²⁺ allows actin and myosin interaction

Question 2

Describe the ventricular action potential

Answer 2

V-gated Na⁺ channels open, depolarisation

Na⁺ channels inactive and there is transient outward K⁺ current - initial repolarisation

V-gated Ca²⁺ channels open (L-type), which slowly inactive following activation

Ca²⁺ channels inactive and V-gated K⁺ channels open

Question 3

Describe the functioning of the SA node and its action potential

Answer 3

SA node cells have no resting potential, becoming active when voltage returns to -60mV

There is slow depolarisation due to slow current of Na⁺, this is the pacemaker potential

Reaches threshold and V-gated Ca²⁺ open (L-type)

Both calcium and sodium channels close and V-gated potassium channels open- repolarisation

Question 4

What is the pacemaker potential and what channels are involved

Answer 4

The initial slop to threshold (funny current)

Activated at potentials more negative than -50mV

HCN channels- hyperpolarisation-activated cyclic nucleotide-gated channels. These allow Na⁺ influx, depolarising cells

Question 5

Why does the SA node set the rhythm of the heart and what happens if it stops

Answer 5

SA node is the fastest to depolarise so acts as pacemaker

If SA node stops or connection is lost then the AV node will depolarise and cause contraction, setting the rhythm

Question 6

What are the pathologies associated with abnormal firing of action potentials

Answer 6

Too slow - bradycardia (less than 60 at rest)

Fail to fire - asystole

Too quickly - tachycardia (greater than 100 at rest)

Become random - fibrillation

Question 7

What is hyperkalaemia and what are its affects and treatments

Answer 7

When plasma potassium is too high >5.5mmol/L

It depolarises the myocytes and slows the upstroke of the action potential. There is inactivation of some sodium channels as membrane potential depolarises due to the increased plasma potassium.

Can lead to slowing or stopping of the heart (asystole due to inactivation of sodium channels)

Treament - calcium gluconate, insulin + glucose

Question 8

What is hypokalaemia and what are its affects

Answer 8

Plasma potassium concentration is too low <3.5mmol/L

It lengthens the action potentail and delays repolarisation. Longer action potentail can lead to early after depolarisations (EADs). This can lead to oscillations in membrane potentail and ventricular fibrillation or tachycardia.

Question 9

Describe how depolarisation leads to an increase in cytosolic Ca²⁺ ion concentration

Answer 9

Depolarisation opens L-type Ca²⁺ channels in T-tubule system

Ca²⁺ entry opens CICR channels in SR
Close link between L-type channels and Ca²⁺ release channels

Ca²⁺ enters across sarcolemma and from SR

Question 10

Describe the process of excitation-contraction coupling in the vascular system

Answer 10

Depolarisation opens VGCCs

Ca²⁺​ enters cell and binds with CaM (4 Ca²⁺​ ions bind)

CaM-Ca²⁺​ complex then binds with MLCK which then phosphorylates the myosin II head in the smooth muscle cell using ATP, to activate the myosin head so it can bind to actin.

MLCP deactivates the head by dephosphorylating the head

Noradrenaline can cause contraction by binding with alpha-1 receptors which releases IP₃ which can release SR Ca²⁺​. DAG from the receptor activates PKC which them phosphorylates MLCP to inactivate it

Question 11

How is contraction in VSM regulated

Answer 11

MLCK can be phosphorylated by PKA, this inhibts its action so inhibits phosphorylation if myosin light chain inhibiting contraction