Session 5

Question 1

Explain how action potential open Ca2+ channels

Answer 1

The action potential arrives at the nerve terminal then depolarisation occurs opening the voltage gated Ca2+ channels to produce an influx of Ca2+ into the nerve.

Question 2

Describe some aspects of Ca2+ channel diversity and function

Answer 2

Intracellular Ca2+ is so low, a small influx will cause a significant increase in intracellular Ca2+
L- Dihydropyridines (blocker)- muscle, neurone, lung
N- Conoxotin (blocker)- neurones
P/Q- Agatoxin (blocker)- neurones
R- Ni2+ (blocker)- neurones/heart
T- Ni2+ (blocker)- neurones

Question 3

Describe events underlying fast synaptic transmission

Transmitter release

Answer 3

1) An action potential causes an influx of Ca2+ through voltage-gated channels which triggers neurotransmitter release via exocytosis
2) Ca2+ binds to Synaptotagnin
3) Vesicles are brought close to the membrane
4) The snare complex makes fusion pores
5) The contents of the vesicle diffuse into the synaptic cleft

Question 4

Describe events underlying fast synaptic transmission

Ach activates Nicotinic AcH receptors on the muscle membrane

Answer 4

1) AcH binds to ligand-gated nicotinic Ach receptors on the post-junctions muscle membrane to produce a depolarisation= end-plate potential
2) Depolarisation raises the adjacent membrane above threshold so the action potential is initiated in the muscle

Question 5

Describe some properties of ligand gated ion channels

Answer 5

A conformational change occurs in the transmembrane protein complex only upon ligand binding.
It is selective for certain ions

Question 6

Explain how neuromuscular blocker D tubocurarine works

Answer 6

Competitive block- D-tubocurarine
(Blocks without triggering action potential)
When the Ach binds to the ligand gated nACHR then leaves, the D-TC competitively blocks the binding site. This will cause the channels to stay closed and cause inhibition of muscle contraction. This will decreases the amplitude of the action potential which will reduce the propogation

Question 7

Explain how neurotransmitter succinylcholine works.

Answer 7

Depolarising
The succinylcholine is favoured by the nACHR and cannot be degraded by the ACH esterase hence depolarisation will be maintained. This will fail to activate adjacent Na+ channels because they have become inactivated.
Fasiculations occurs

Question 8

What effect would you expect on the action potential if the voltage gated Na+ channels are blocked?

Answer 8

The action potential wouldn’t be able to propagate along the axon and it wouldn’t be able to depolarise the membrane much.

Question 9

How might a drug act to block the production of action potentials?

Answer 9

• Some will act at the post-synaptic neurotransmitter receptors e.g nicotinic
• Some will act on the enzymes in the synaptic cleft- organophosphate poisoning
• Some will act on voltage gated sodium channels throughout the axon

Question 10

What is meant by the absolute refractory period and relative refractory period of a nerve fibre?

Answer 10

Absolute refractory period- no action potential can be made at all even if there is an increase in stimulus from when it is initiated until Na+ becomes active again
Relative refractory period- A second action potential can be initiated but will require a greater stimulus than before the refractory periods

Question 11

Properties of action potential

Answer 11

• Change in voltage across membrane
• Only occurs if a threshold level is reached
• All or nothing
• Propagated without loss of amplitude

Question 12

What is ‘all or nothing’?

Answer 12

Action potential can only occur if the threshold value is met/exceeded.
Below this, nothing will happen.

Question 13

What does Na+ becoming inactive mean?

Answer 13

A protein complex blocks the pore, so it doesn’t allow any sodium ions to flow in any direction

Question 14

What is hyperpolarisation during the action potential and how does it occur?

Answer 14

Getting the membrane potential back to the resting membrane potential after it has fallen too negative
Done by Na+/K+ ATPase

Question 15

How is propogation of the action potential a positive feedback loop?

Answer 15

Depolarisation of the membrane causes more Na+ channels to open

Question 16

Describe some molecular properties of Voltage gated Sodium and Potassium channels

Answer 16

Sodium- One alpha subunit consist of four similar section/repeats. Pore region. S4- voltage sensor. Inactivation particle
Potassium- Four individual alpha subunits. S4 voltage sensor. Pore region

Question 17

How does the pore region contribute to selectivity?

Answer 17

The amino acid sequence will determine the selectivity when it is open

Question 18

When is it easier for the Local anaesthetic to block Na+ channels?

Answer 18

Procaine-

1) When the channel is open
2) There is a higher affinity to the inactivate state of the Na+ channel.
3) The protonated form gets attracted through the hydrophillic pathway

Question 19

What is conduction velocity?

Answer 19

Speed at which an electrical impulse propagates down a neural pathway

Question 20

How do we measure the conduction velocity?

Answer 20

Speed equals distance over time
Distance- between stimulating electrode and recording electrode
Time- Time gap between stimulus and action potential registered by recording electrode

Question 21

When measuring the conduction velocity why are there multiple peaks?

Answer 21

You have multiple diameter axons with different conduction velocities
Larger diameter, faster conduction velocity

Question 22

Local circuit theory

Answer 22

1) Inject positive ions
2) Repel positive ions and attract negative ions
3) Produce a local+ immediate depolarisation of the axon
4) Depolarisation decreases from the point of injection

Question 23

What is the length constant?

Answer 23

Distance taken for the potential to fall to 37% of its original value

Question 24

What membrane resistance have to do with ion channels?

Answer 24

Lower resistance, more ion channels open

Question 25

Explain the implications of myelination for conduction

Answer 25

1) Reduces Capacitance
2) Creates a larger diameter
Hence larger area of axon, indirectly proportional to resistance hence a smaller resistance. Increases the conduction velocity

Question 26

What is saltatory conduction?

Answer 26

Action potential moves from node to node

Question 27

Explain why myasthenia gravis causes weakness

Answer 27

Autoimmune disease
Antibodies directed against the nACHR receptor
Which causes:
1) Loss of functional nACHR by complement mediated cell lysis
2) Receptor degradation
End-plate potentials are reduced in amplitude leading to muscle weakness and fatigue