Session 5 - Electrical excitability: Action potentials and the neuromuscular junction

Question 1

Outline 5 properties of an action potential

Answer 1

• change in voltage across membrane
• Depends on ionic gradients and relative permeability of the membrane
• Only occurs if a threshold level is reached
• All or nothing
• Propagated without loss of amplitude

Question 2

Is the action potential in all excitable cells the same?

Answer 2

No, the action potential varies vastly from as axon to the Sino-atrial node. As a result of their ion different permeabilities

Question 3

To produce an action potential how many ions need to move?

Answer 3

A relatively small amount relative to the charge

IE: in an axon of diameter 1 and 10 the [Na+]% change is 0.4% and 0.04% respectively

Question 4

Describe the positive feedback loop when the membrane exceeds the threshold potential

Answer 4

• Depolarisation to threshold
• Voltage gated Na+ ions channels open
• Membrane is depolarised further stimulating more Na+ channels to open

This occurs until all the Na+ equilibrium is nearly reached and all the Na+ voltage gated channels are inactivated

Question 5

Describe what happens during repolarisation of the action potential.

Answer 5

• Depolarisation
  1) Opens voltage gated K+ channels and inactivated Na+ channel
  2) This results in the efflux of K+ and the movement of Na+ is stopped
  3) This repolarises the membrane

Question 6

What role does the Na+/K+ ATPase pump have in an action potential?

Answer 6

The Na/K pump is NOT involved in the repolarisation it only restores the [K+] and [Na+] when hyperpolarisation occurs. It is crucial to realise that this deosn’t need to happen to allow for another AP only that it will occur over a relatively long time frame. (The concentration differences are so small as long as the membrane potential returns another AP can be formed)

Question 7

Describe the Absolute and Relative refractory periods. Give relative times for these in a nerve.

Answer 7

ARP - During ARP no stimulus can initiate an action potential as all the Na+ voltage gated channels are inactivated. (1ms)
RRP - During the RRP a stronger than normal stimulus can initiate an action potential. This is because more Na+ channels are recovering from inactivation and K+ channels are closing (4ms)

Question 8

What are the relative action potential durations and sizes in different tissues?

Answer 8

Axon: Duration = 0.5ms Size = -70mV to +30mV
Skeletal Muscle: Duration = 0.5ms Size = -90mV to +40mV
Sino-atrial Node: Duration = 100ms Size = -60mV to +30mV
Cardiac Ventricle: Duration = 100ms Size = -90mV to +30mV

Question 9

Where on an axon are will an action potential be triggered if it exceeds the threshold and why?

Answer 9

Axon Hillock

This is where the sum of all the stimuli can be amounted (combination of small, large and inhibitory PSP)

Question 10

What’s the difference between a Na+, Ca2+ and K+ voltage gated ion channel structure?

Answer 10

All have 4 homologous repeat units
Each repeat had 6 transmembrane domains 1 being voltage sensitive

Difference - Ca2+ and Na+ repeat units are bound together whereas K+ all 2 repeats are individual Alpha units

Question 11

How do local anaesthetics work and give a named example?

Answer 11

Lidocaine - block Na+ channels to disrupt action potential propagation

1) transverses the membrane in it’s unprotonated form and either directly enters the channel or enters the cytoplasm
2) Becomes protonated and blocks the channel

Question 12

In what order do local anaesthetics block axons?

Answer 12

1) Small myelinated axons
2) Unmyelinated axons
3) Large myelinated axons

Question 13

?Why is it important Na+ channels are inactivated?

Answer 13

• To allow for the rapid switch off of the action potential

- Allows for inactivation of Na+ channels and as such a refractory period for propagation of an action potential

Question 14

What is the consequence of the delayed closing of voltage gated K+ channels?

Answer 14

Ensures the hyperpolarisation of the cell to a larger degree which allows for faster reactivation of the Na+ channels

Question 15

Why is Na/K pump NOT involved in producing the action potential?

Answer 15

Very little flow of ions. So there to maintain gradient.

Question 16

What is the length constant with respect to an action potential?

Answer 16

the distance it takes for the potential to fall to 37% of it’s original value

Question 17

What properties lead to a high conduction velocity?

Answer 17

1) A high membrane resistance
2) A low membrane resistance
3) A large axon diameter (low cytoplasmic resistance)

Question 18

How does the myelin sheath act to increase the length constant?

Answer 18

The myelin sheath acts as a good insulator (by blocking the Na+ channels increasing the membrane resistance)

1) large increase in membrane resistance
2) large decrease in membrane capacitance
3) These increase length constant
4) slightly decrease in time constant

Question 19

Why does multiple sclerosis effect people in many different ways?

Answer 19

The demyelination of the axons in the CNS can occur in any place there is no specific place as such it can effect people in many different way

Question 20

What effect does demyelination have?

Answer 20

Demyelination decreases the length constant as resistance is decreased and capacitance is increased. This means that when the action potential reaches the next node it fails to reach the threshold and the AP is stopped.

Question 21

Surmise action potential generation

Answer 21

1) Depolarisation to threshold triggers opening of many voltage gated Na+ channels
2) Na+ influx produces the upstroke of the action potential (membrane potential to ENa)
3) This depolarisation causes inactivation of Na+ channels and opening of K+ channels
4) Na+ influx stops and K+ efflux leads to repolarisation (potential to Ek)
5) relatively few ions move and Na/K pump NOT involved in repolarisation

Question 22

Name some diseases that effect myelination and why the CNS and PNS are distinct diseases.

Answer 22

CNS - Multiple sclerosis (all CNS nerves)
- Devic’s disease - optic nerve and spinal cord

PNS - Laundy-Guilllian-Barre syndrome
- Charlotte-Marie-Tooth Disease

CNS and PNS are effected in distinct diseases as they are myelinated by different cells. CNS by oligodendrocytes and PNS by Schwann cells

Question 23

What happens at the nerve terminal of a neuromuscular junction?

Answer 23

1- Action potential stimulates opening of Ca2+ voltage gated channels
2- Influx of Ca2+ ([Ca2+] increases)
3) stimulates the exocytosis (release) of neurotransmitter

Question 24

What effect does the increased frequency of action potentials have on the nerve?

Answer 24

It increases Ca2+ influx and as such increased transmitter release (generating a greater stimulus)

Question 25

What effect does the neurotransmitter have on the muscle end plate?

Answer 25

1) neurotransmitter (ACh) diffuses across cleft
2) ACh binds to nAChR which are lingand gated ion CATION channels
3) Depolarisation propagated along muscle as Na+ channels open

Question 26

How does d-Tubocurarine work?

Answer 26

It blocks the nAChR by competitive inhibition. It can be overcome by increasing the concentration of ACh

Question 27

How does succinylcholine work?

Answer 27

Succinylcholine inactivates Na+ channels resulting in the failure to propagate the depolarisation

Question 28

Why is it so important to get general anaesthetics and neuromuscular blockers in the correct quantities for a surgery?

Answer 28

A person paralyzed with a neuromuscular blocker looks similar to a person under general anaesthetic - but though they will feel pain they are unable to speak or move.

Question 29

What occurs in myasthenia gravis and how does the edrophonium test work?

Answer 29

This is an autoimmune disease which targets nAChR. As such end-plate potentials fail to reach threshold and trigger an AP.
Edrophonium chloride, a short acting anticholinesterase, allows ACh to act bind to greater proportion of receptors before being broken down and as such removes the symptoms

Question 30

What is the effect of organophosphate poisoning?

Answer 30

They act as acetylcholinesterase inhibitors that form a stable and irreversible covalent bond to the enzyme.
As such this results in over stimulation of AChR.
Recovery takes weeks as new enzymes have to be produced to replace the effected ones

Question 31

What is the difference between mAChR and nAChR and where are they found?

Answer 31

nAChR - fast depolarisation as it’s a ligand gated ion channel
mAChR - produced slower response as are linked to G proteins. They are found in the parasympathetic nervous target tissues