Electrical And Mechanical Mechanisms

Question 1

What sets the resting membrane potential?

Answer 1

K+ permeability sets the resting membrane potential.

Cardiac myocytes are permeable to K+ ions at rest.

K+ ions move out of the cell - down their conc. gradient

Small movement of ions make the inside negative with respect to the outside.

As charge builds up, an electrical gradient is established.

Question 2

Why does resting membrane potential not exactly equal Ek?

Answer 2

This is because there is a very small permeability to other ion species at rest.

Ek= -95mv RMP of cardiac myocytes = -90- -85mv

Question 3

How do action potentials lead to contraction in cardiac myocytes?

Answer 3

When cardiac myocytes release action potential, they trigger an increase in systolic conc. of Ca2+

A rise in Ca is required to allow actin and myosin interaction. This generates tension and therefore contraction.

Question 4

How does a ventricular action potential occur?

Answer 4

Depolarisation caused by opening of Voltage Gated Na⁺ channels

Transient outward K+ current

Opening of Voltage Gated Ca2+ channels (some K+ channels are also open)

Ca2+ channels inactivate (L type Ca ion channels that gradually inactivate) and Voltage Gated K⁺ channels open.

The resting membrane potential is due to background K⁺ channels.

Question 5

Describe the SA node action potential.

Answer 5

Pacemaker potential is a slow depolarisation to threshold due to the funny current. (This funny current is activated at about -60mV).

It is permeable to K and Na ions but tend to get more Na ions in.

Then, opening of voltage gated Ca2+ channels.

Next, Opening of voltage gated K+ channels to repolarise.

Voltage gated Na ion channels would be inactivated as the membrane potential does no go negative enough so they cannot work. Instead, they use Ca2+ channels to cause depolarisation.

Question 6

What type of channel is responsible for the funny current?

Answer 6

HCN channel. Hyperpolarisation-activated, Cyclic Nucleotide-gated channels. This allows the influx of Na+ channels which results in depolarisation the cell (by the influx of Ca ions).

Question 7

What is the membrane potential of the SA node?

Answer 7

It has an unstable membrane potential because of I_f (funny current). This is the pacemaker potential (slow depolarisation until threshold is reached).

Question 8

Why does the SA node set the cardiac rhythm?

Answer 8

As the SA node is fastest to depolarise. (other parts are automatic but are slower)

AVN is next.

It is also the pacemaker.

Question 9

How do action potentials differ throughout the heart?

Answer 9

Question 10

What is the term if action potentials fire too slowly?

Answer 10

Bradycardia

Question 11

What is the term if action potentials fail?

Answer 11

Asystole

Question 12

What is the term if action potentials fire too quickly?

Answer 12

Tachycardia

Question 13

What is the term if electrical activity becomes random?

Answer 13

Fibrillation

Question 14

What is normal plasma K+ conc?

Answer 14

3.3-5.5mmol/L

If too high or too low, can cause problems, particularly for the heart (hyperkalemia / Hypokalemia).

Question 15

Why are cardiac myocytes so sensitive to K+ conc outside cell?

Answer 15

Because K⁺ permeability dominates ventricular resting potential.

The heart has many different types of K⁺ channels and some behave in a peculiar way.

Question 16

What are the effects of hyperkalcaemia?

Answer 16

Hyperkalaemia depolarises the myocytes and slows down the upstroke of the action potential.

This is because, if you raise plasma K then E_k gets less negative so the membrane potential depolarises a bit.

This inactivates some of the voltage gated Na⁺ channels which slows the upstroke.

Question 17

What are the risks of hyperkalaemia?

Answer 17

• The heart can stop - asystole
• May initially get an increase in excitability.
• Depends in th extend and how quickly it occurs.
• Mild 5.5 - 5.9 mmol/L
• Moderate 6-6.4 mmol/L
• Severe >6.5mmol/L

Question 18

What are the treatments of hypercalcaemia?

Answer 18

Calcium gluconate

Insulin (this increases K+ in the cells) + glucose

BUT, these won’t work if the heart has already stopped.

Question 19

Wha are the effects of hypokalaemia?

Answer 19

Action Potential lasts longer.

Especially ventricular part.

This delays repolarisaion.

This can lead to early after depolarisations (EADs)

Which can lead to oscillations in membrane potential.

This can result in ventricular fibrillation.

Question 20

What is excitation contraction coupling?

Answer 20

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

Localised Ca2+ entry opens CICR (calcim-induced calcium released) channels in the SR.

Close link between L-type channels and Ca²⁺ release channelas

25% enters across the sarcolemma and 75% released from SR

Question 21

How is cardiac myocytes contraction regulated?

Answer 21

Ca2+ bonds to troponin C

Conformational change shits tropomyosin to reveal myosin binding site on actin filament.

Sliding filament.

Question 22

How do cardiac myocytes relax?

Answer 22

Must return conc. Ca²⁺ to resting levels

Most is pumped back into SR (SERCA) (raised Ca stimulates the pumps)

Some exits across cell membrane

• Sarcolemmal Ca²⁺²ATPase
• Na+Ca2+ exchanger

Question 23

How are the tone of blood vessles controlled?

Answer 23

Tone of blood vessels is controlled by contraction and relaxation of vascular smooth muscle cells which are located in tunica media and Present in arteries, arterioles and veins.

Question 24

What is the myosin light chain?

Answer 24

Activation of the myosin light chain allows interaction with actin.

Myosin light chain must be phosphorylated to enable actin-myosin interaction / binding.

Question 25

How is contraction regulated in vascular smooth muscle?

Answer 25

Ca2+ binds to calmodulin

• This activates the Myosin Light Chain Kinase (MLCK)
• MLCK phosphorylates the myosin light chain to permit interaction with actin.

Relaxation as Ca⁺² levels decline

• Myosin light chain phosphatase dephosphorylates the myosin light chain.

(MLCK itself can itself can be phosphorylated)

Phosphorylation of MLCK by PKA inhibits the action of MLCK.

• Therefore inhibits phosphorylation of the myosin light chain and inhibits contraction.

Question 26

What are the differences between cardiac and smooth muscle?

Answer 26

Contraction in the heart is initiated by spread of APs from SA node.

Cardiac myocytes action potentials allows Ca2+ entry

• further Ca2+ released from SR
• Increased intrcellular Ca2+
• Ca2+ binds to troponin-C

Contraction of vascular smooth muscle cells initiated by depolarisation or activation of a-adrenoreceptors.

• Increased intracellular Ca2+
• Ca2+ binding to calmodulin.
• Activation of MLCK - phosphorylase myosin light chain.