Week 4 - Action Potential and Conduction of the Nerve Impulse

Question 1

What are action potentials?

Answer 1

A change in voltage across the membrane

• Only occur if the threshold value is reached
• Propagated without loss of amplitude
• All or nothing
• They are generated by an increase in permeability to Na+, which brings the membrane close to the Na+ equilibrium potential (Ena)

Question 2

What do action potentials depend on?

Answer 2

• Ionic gradients (movement of Na+ and K+)

- Relative permeability

Question 3

Which ion channels are used in nervous transmission?

Answer 3

Voltage-gated Na+ and K+ channels

• Depolarisation causes them to open
• Once a certain membrane potential (threshold potential) is reached a positive feedback occurs as Na+ channels begin to open

Question 4

What is the ‘all or none’ characteristic of the action potential?

Answer 4

• If the membrane depolarisation reaches the threshold value, then an action potential will occur
• If it does not reach the threshold value then no action potential will be produced

Question 5

What happens after depolarisation of the membrane?

Answer 5

• K+ channels are opened
• K+ efflux
• Na+ channels are inactivated
• Na+ influx is stopped

Question 6

What does ‘inactivation of a Na+ channel’ mean?

Answer 6

There is an inactivation molecule
There is an outer gate
- Shut at resting potential
- Opens as the membrane potential depolarises, allowing Na+ through
- It closes during inactivation
There is an inner gate
- Open at resting potential
- When the membrane depolarises, Na+ can pass through it
- As the membrane becomes more positive, the inner gate gradually shuts
- It shuts completely during inactivation

Question 7

What happens if the conductance to an ion is increased?

Answer 7

The membrane potential will move closer to the equilibrium potential for that ion
- The conductance of the membrane to a particular ion is dependent on the number of channels that are open for the ion

Question 8

What is the absolute refractory period?

Answer 8

When nearly all the Na+ channels are in the inactivated state, so the membrane is unexcitable

Question 9

What is the relative refractory period?

Answer 9

Na+ channels are recovering from inactivation

- The excitability returns towards normal as the number of inactivated channels decreases

Question 10

How are Na+ and Ca2+ channels similar?

Answer 10

• Main pore forming subunit is 1 peptide consisting of 4 homologous repeats
• Each repeat consists of 6 transmembrane spanning domains
• 1 of these domains is able to sense the voltage field across the membrane

Question 11

Describe voltage-gated K+ channels

Answer 11

• Similar in structure to Na+ and Ca2+ channels, except each repeat is in fact a separate subunit
• A functional channel requires 4 subunits
• Each subunit still has 6 transmembrane domains, 1 of which is voltage sensitive

Question 12

How do local anaesthetics act?

Answer 12

By binding to and blocking Na+ channels

• This stops generation of an action potential
• They only affect open Na+ channels

Question 13

What do local anaesthetics block?

Answer 13

In the following order:

• Small myelinated axons
• Un-myelinated axons
• Large myelinated axons

Question 14

What is accommodation?

Answer 14

The longer the stimulus, the larger the depolarisation necessary to initiate an action potential

• The threshold value is reached, but over a very long time and very gradually
• The Na+ channels have open, but by the time the threshold value has been reached they have been inactivated
• Hence no action potential is fired

Question 15

How can you do extracellular recording of electrical activity?

Answer 15

Electrical stimulation
- Occurs under a cathode (excitability will be reduced under an anode)
- This can be used to stimulate an axon or group of axons to threshold, thus initiating an action potential
Recording
- Record changes in potential between the stimulating (cathode) and recording (anode) electrodes along an axon, and the time gap between the stimulus and action potential
- Conduction velocity can be calculated (distance/time)

Question 16

How is an action potential conducted along an axon?

Answer 16

A change in membrane potential in 1 part can spread to adjacent areas of the axon

• This occurs because of local current spread (local circuit theory of propagation)
• When local current spread causes depolarisation of part of the axon to threshold, then an action potential is initiated in that location

Question 17

How is the conduction velocity affected?

Answer 17

Determined by how far along the axon these local currents can spread

• The further it spreads, the faster the conduction velocity of the axon will be
• Affected by properties of the axon
• Myelination

Question 18

What properties of the axon lead to a high conduction velocity?

Answer 18

• A high membrane resistance
• A low membrane capacitance
• A large axon diameter (leads to a low cytoplasmic resistance)

Question 19

What is capacitance?

Answer 19

The ability to store charge

- A high capacitance takes more current to charge

Question 20

What does membrane resistance depend on?

Answer 20

The number of ion channels open

- The lower the resistance, the more ion channels are open

Question 21

Explain the local circuit theory of propagation

Answer 21

• The depolarisation of a small region of membrane produces transmembrane currents in neighbouring regions
• As Na+ channels are voltage-gated, this opens more channels, causing the propagation of the action potential
• These local currents cause the action potential to propagate down the axon
• It is faster than action potential spread over the axonal membrane

Question 22

How is conduction velocity linked to fibre diameter?

Answer 22

• Myelinated: velocity is proportional to diameter

- Unmyelinated: velocity is proportional to the square root of the diameter

Question 23

How does myelination affect conduction velocity?

Answer 23

Myelin reduces the capacitance and increases the resistance of the axonal membrane
- This increases conduction velocity

Question 24

What is saltatory conduction?

Answer 24

Occurs in myelinated nerve fibres

• Due to the reduced capacitance in the internodal region, the local axonal current (induced by an action potential at a node of Ranvier) spreads further down the axon to depolarise the next node without firing an action potential in the internodal region
• Nerve conduction occurs in a ‘jumping’ manner down the nerve
• This greatly increases conduction velocity

Question 25

What happens in regions of demyelination?

Answer 25

The density of the action potential current is reduced

• This is because of resistive and capacitive shunting
• Threshold value cannot be reached, so no action potentials are produced

Question 26

What diseases are there in the PNS that involve areas of some axons losing their myelin sheath?

Answer 26

• Laundry-Guillain-Barre Syndrome

- Charcot-Marie-Tooth disease

Question 27

What diseases are there in the CNS that involve areas of some axons losing their myelin sheath?

Answer 27

• Multiple sclerosis (all CNS nerves)

- Devic’s disease (optic and spinal cord nerves only)

Question 28

Describe multiple sclerosis

Answer 28

Myelin is destroyed in certain areas of the CNS

• This can have dramatic effects on the ability of previously myelinated axons to conduct action potentials properly
• Can lead to decreased conduction velocity, complete block or cases where only some action potentials are transmitted