Session 5 - The Action potential

Question 1

• Describe the properties of the action potential
• Explain the ionic basis of the action potential
• Explain how the ionic permeability of the membrane alters with time
• Describe some molecular properties of ion channels
• Explain how local anaesthetics have their effects
• Describe how conduction velocity can be measured
• Explain the local circuit theory of propagation
• Explain how conduction velocity is linked to fibre diameter
• Explain the implications of myelination for conduction
• Describe certain consequences of demyelination

Question 2

Describe the properties of the action potential LO (5)

Answer 2

• 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 3

Draw and give th RMP for axons, skeletal muscle, SA node and cardiac ventricular muscle

Answer 3

Question 4

1. If the conductance (g) to any ion is increased the membrane potential (Vm) will ?
2. The conductance of the membrane to a particular ion is dependent on ?

Answer 4

1. move closer to the equilibrium potential for that ion
2. the number of channels for the ion that are open.

Question 5

Explain the ionic basis of the action potential

Question 6

Explain how the ionic permeability of the membrane alters with time during an AP

Answer 6

Question 7

Describe the Channel activity during an axonal action potential

Answer 7

Question 8

What is the ARP and RRP?

Answer 8

ARP - nearly all Na+ channels are in the inactivated state (no AP)

RRP - Na+ channels are recovering from inactivation, the excitability returns towards normal as the number of channels in the inactivated state decreases (maybe AP)

Question 9

After the Na+ channels are opened, how can they open again?

Answer 9

Generally require K+ to go from inactivated to closed. So a change in mp can cause them to open again.

Question 10

Describe some molecular properties of ion channels LO

What is the structure for voltage gated Na+ channels

Answer 10

• 1 peptide
• inactivation particle -> acts as a ply
• 4th traansmembrane domain is has positive aa - change in mp = conformational change
• p region -> dictate what ions go through the channel

Question 11

Describe some molecular properties of ion channels LO

What is the structure for voltage gated K+ channels

Answer 11

P = selectivity filter

4 subunits to make a functional potassium channel but only one subunit for a functional sodium channel

S4= Conformational change

Question 12

Explain how local anaesthetics have their effects LO

Local anaesthetics such as procaine act mainly by ?

Answer 12

blocking Na+ channels.

Question 13

Local anaesthetics block in the following order:

Answer 13

1. small myelinated axons
2. un-myelinated axons
3. large myelinated axons

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Question 14

What is this image showing?

Answer 14

how the local anaesthetic/ blocker cna block Na+ channels more easily when it is open and remains there in the inactive state

Question 15

Describe how conduction velocity can be measured LO

Answer 15

Speed AP has to travel from the point of stimulus to get to different regions

• take into account the distance
• take into account the time
• work out conduction velocity

Question 16

Why are the conduction velocities different?

Question 17

Explain the local circuit theory of propagation LO

Answer 17

Injection of current into an axon will cause the resulting charge to spread along the axon and cause an immediate local change in the membrane potential.

But how far does this change in the membrane potential spread ?

Question 18

1. Capacitance, C, is the?
2. The membrane resistance depends on?

Answer 18

1. ability to store charge. This is a property of the lipid bilayer
2. the no. of ion channels open. The lower the resistance the more ion channels are open.

Question 19

1. Spread of local current depends on ?

Answer 19

1. membrane resistance and capacitance

Question 20

1. High capacitance –
2. High resistance –

Answer 20

1. High capacitance – voltage changes more slowly in response to current injection
2. High resistance – change in voltage spreads further along the axon

Question 21

Function of:

1. Aα –
2. Aδ –
3. B –
4. C –

Answer 21

1. Aα – sensory fibres from muscle spindles, motor neurones to skeletal muscle
   ​2. Aδ – sensory fibres from pain and temperature receptors (sharp localized pain)
2. B – preganglionic neurones of autonomic nervous system
3. C – sensory fibres from pain, temperature and itch receptors (diffuse pain)

Question 22

What is this image showing?

Answer 22

• Local currents cause the propagation of the action potential (The first AP spreads the second AP is over threshold)
• the period after the AP is refractory thus an AP can only travel in one direction

Question 23

Explain how conduction velocity is linked to fibre diameter LO

Answer 23

Wider diameter axons will conduct faster

Question 24

Explain the implications of myelination for conduction LO

1. What is myelin?
2. What are Na+ channels concentrated in myelinated axons?
3. Function of the myelin sheath

Answer 24

1. Myelin is a sheath of tightly packed membrane
2. Nodes of Ranvier
3. Insulation

saltatory conduction

Inc conduction velocity

AP only at nodes of Ranvier

Question 25

What is the effect of myelinated and unmyelinated axons of conduction velocity

Answer 25

Question 26

Myelin sheath improves conduction by:

Answer 26

Question 27

Describe certain consequences of demyelination LO _Disease states affecting conduction of the action potential_ 1. Central Nervous System e.g. 2. Peripheral Nervous System e.g. These diseases result from ?

Answer 27

1. • Multiple sclerosis – all CNS nerves (most common) • Devic’s disease – optic and spinal cord nerves only 2. • Landry-Guillain-Barre syndrome • Charcot-Marie-Tooth disease **breakdown or damage the myelin sheath**

Question 28

Explain why there is no or little conduction of an AP in demyelinating diseases

Answer 28

- local current spread depolarizes next node above threshold - In regions of demyelinaion the density of the action current is reduced because of resistive and capacitive shunting.

Question 29

Generation of the action potential (5)

Answer 29

• depolarization to threshold triggers the opening of many voltage-gated Na+ channels • the influx of Na+ produces the rapid upstroke of the action potential (membrane potential moves towards ENa) • this depolarization causes inactivation of Na+ channels and opening of voltage- gated K+ channels • Na+ influx stops and the increased K+ efflux leads to repolarization (membrane potential moves towards EK) • relatively little ions move and the Na/K ATPase is NOT involved in action potential repolarization

Question 30

Conduction of the action potential

Answer 30

* an action potential causes local current flow leading to an immediate depolarization of adjacent bits of the axon * where this local depolarization reaches threshold an action potential is initiated • the spread of this local change in the membrane potential is increased by a high membrane resistance and low membrane capacitance – the longer this distance the faster the conduction * myelinated axons have a high membrane resistance and low membrane capacitance * at nodes of Ranvier, between the myelin sheaths, the axon is bare and the membrane has a high concentration of Na+ channels * the action potential jumps from node to node – termed saltatory conduction, which is faster than that in unmeylinated axons * damage to the myelin (e.g. in multiple sclerosis) can stop saltatory conduction

Question 31

_Electrical exitability - synaptic transmission and the neuromuscular junction_ * Explain how action potentials open Ca2+ channels * Describe some aspects of Ca2+ channel diversity and function * Describe events underlying fast synaptic transmission * Describe some properties of ligand gated ion channels * Explain how neuromuscular blockers work * Explain why myasthenia gravis causes weakness

Question 32

The neuromuscular junction is ?

Answer 32

the synapse between a nerve and a **skeletal** muscle fibre. ​

Question 33

What happens at the nerve terminal ?

Answer 33

Explain how action potentials open Ca2+ channels LO

Question 34

1. Increasing frequency of action potentials has what effect on Ca2+ entry?

Answer 34

1. increases amount of nerve terminal Ca2+ entry

Question 35

Describe some aspects of Ca2+ channel diversity and function LO

Question 36

The structure of the α-subunit of voltage-gated Ca2+ channels is very similar to voltage-gated Na+ channels, how?

Answer 36

- 1 peptide = one functional subunit

Question 37

Which calcium isoforms will we most commonly appreciate

Answer 37

L -type Nifedipine -\> less Ca2+ entry -\> useful for high bp as less contraction of arteries

Question 38

Answer 38

A pore forming subunit is necessary for a functional channel Other associated subunits fine-tune the properties and enable correct regulation of channel activity

Question 39

_Properties of Ca2+ channels_ 1. How does activation of Voltage-gated Ca2+ channels differ from voltage gated Na+ channels? 2. How does activation of Ca2+ channels differ from Na+ channels? 3. Ca2+ channel inactivation is ?

Answer 39

1. activate more slowly than voltage-gated Na+ channels 2. Ca2+ channels activate and inactivate – but much more slowly than Na+ channels 3. Ca2+-dependent

Question 40

Answer 40

Question 41

Answer 41

Question 42

Transmitter release:​

Answer 42

* Ca2+ entry through Ca2+ channels * Ca2+ binds to synaptotagmin * Vesicle brought close to membrane * Snare complex make a fusion pore * Transmitter released through this pore

Question 43

Release of ACh activates nicotinic ACh receptor channels what ions can pass through this channel? Which ions significantly pass through?

Answer 43

Question 44

How does the end-plate potential initiate a muscle action potential?

Answer 44

- ACh released binds to nAChR - influx of Na+ causes depolarisation (moves to ENa) - ACh degraded by ACh esterase - Depolarisation results in activation of adjacent volatage gated Na+ channels

Question 45

Explain how neuromuscular blockers work LO Give 2 examples of Blockers of nicotinic ACh receptors

Answer 45

Question 46

Explain how tubocurarine works

Answer 46

Question 47

Can the effect of tubocurarine be overcome?

Answer 47

The block by d-TC can be overcome by increasing the concentration of ACh

Question 48

Explain how succinylcholine works

Answer 48

Succinylcholine binds to nAChR results in depolarisation -\> opens adjacent Na channels continuous depo from nAChR doesn’t allow for reactivation of adjacent Na channels

Question 49

Explain why myasthenia gravis causes weakness LO Mayasthenia gravis 1. What is it? 2. Symptoms 3. Explain the reasoning for the symptoms

Answer 49

1. an autoimmune disease targeting nACh receptors. 2. • Patients suffer profound weakness • Weakness increases with exercise 3. • Caused by antibodies directed against nAChR on postsynaptic membrane of skeletal muscle • Antibodies lead to loss of functional nAChR by complement mediated lysis and receptor degredation • Endplate potentials are reduced in amplitude leading to muscle weakness and fatigue

Question 50

Summary of transmission at the neuromuscular junction: • Action potential arrives at the motoneurone terminal where it opens voltage-gated Ca2+ channels. * Ca2+ entry initiates exocytosis of vesicles containing ACh. * ACh binds to nicotinic ACh receptors on the muscle end-plate, causes them to open and the flow of cations causes a depolarization called the end-plate potential. * The end-plate potential depolarizes the adjacent muscle membrane and activates voltage-gated Na+ channels, thereby initiating an action potential in the muscle fibre which then contracts due to excitation-contraction coupling. • nACh receptors can be blocked competitively by d-tubocurarine – this causes paralysis. • Drugs such as succinylcholine are known as depolarizing blockers and work by causing inactivation of the Na+ channels adjacent to the neuromuscular junction.

Question 51

Other than nAChR what does ACh bind to? Which part of the NS is this seen?

Answer 51

mAChR = muscarinic ACh receptor

Question 52

Nicotinic and muscarinic ACh receptors operate differently, why?

Answer 52

- nAChR produces a fast depolarization because it is a ligand gated ion channel - mAChR produce a slower response because they are coupled to G- proteins which trigger a cascade of events in the cell.